微RNA参与实体瘤缺氧微环境调控的机制研究
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摘要
作为实体瘤的主要特征之一,缺氧(Hypoxia)通常被精确定义为组织中的氧分压低于5～10毫米汞柱。众所周知,恶性细胞的生长同样需要血管网络为其提供充足的氧和养分,但是肿瘤细胞的恶性增殖总是远远快于血管网络的形成,当组织中的血管网络无法满足肿瘤细胞的生长、代谢的需要时,就形成了局部缺氧的微环境。缺氧微环境能够影响肿瘤细胞的很多生物学特性,其中包括细胞的生长、凋亡、新生血管的生成、转移以及对治疗的敏感性等等。因此深入探讨肿瘤缺氧微环境的形成机制以及肿瘤细胞在缺氧微环境中的应对机制就成为理解肿瘤发生、发展等生理过程的关键所在,而对肿瘤发生、发展过程更深刻的理解又能够促使人们找到肿瘤诊断和治疗的新途径。
microRNAs (miRNAs)是一类长度约为22个核苷酸(nucleotide, nt)的非编码小分子RNA, miRNAs参与了包括细胞分化、增殖、代谢、死亡以及肿瘤生成等在内的一系列的细胞生理和病理进程。近年来大量的研究已经证实,miRNAs与肿瘤的缺氧微环境之间也存在着千丝万缕的联系。相比正常的组织,肿瘤组织中miRNAs的整体表达水平往往会发生巨大的改变,研究人员已经证实,在某些肿瘤中这种改变与肿瘤的临床、病理特征密切相关,但是直到今天,人们还未能对这种变化的意义做出确切的解释,miRNAs在肿瘤缺氧微环境中的调控和作用机制仍然有待于进一步的探索和发现。
为了探讨miRNAs与实体瘤缺氧微环境的相关性及其参与肿瘤发生、发展调控的具体机制,借助于高通量筛查手段——miRNAs芯片,我们对培养于不同氧浓度下的结直肠癌细胞系中miRNAs的表达情况进行检测和鉴定,筛选出了多种在缺氧状态下表达水平发生改变的miRNAs。在此基础之上,进一步通过体外、内实验对其中一些重要的缺氧相关miRNAs的调控和作用机制进行了深入的探讨。我们的研究显示,缺氧状态下培养的p53野生型细胞中miR-17-92簇的表达水平显著下调,而同样在缺氧状态下培养的p53突变型细胞中则没有变化,且这种缺氧依赖性的表达下调并不受已明确的miR-17-92簇转录调控因子c-Myc的控制；通过报告基因检测系统,我们发现miR-17-92簇启动子区的近端存在一个p53结合位点,通过与该位点的结合,p53在缺氧状态下对miR-17-92簇的表达水平进行抑制;免疫共沉淀、重复免疫共沉淀以及定量分析的结果显示,该位点与基本转录元件——TATA框重叠,p53与基本转录因子——TATA结合蛋白能够竞争性的结合于启动子上的这一区域;上调miR-17-92簇的表达能够明显抑制缺氧介导的细胞凋亡,而下调miR-17-92簇中主要成员miR-17-5p和miR-20a的表达会促进缺氧介导的细胞凋亡;以上这些结果都强烈提示,p53依赖性的miR-17-92簇表达下调在缺氧介导的细胞凋亡中发挥着重要的作用,因此我们的发现促进了人们对于p53的肿瘤抑制功能的理解。与此同时,我们还发现肿瘤的缺氧微环境能够导致miR-15-16簇的表达下调,进而影响肿瘤细胞的增殖、凋亡尤其是迁移和侵袭能力;通过结直肠癌原位动物模型,我们发现较高的miR-15-16簇表达水平能够抑制肿瘤的新生血管生成和远端转移(主要是肝转移);进一步的体外、内实验显示,miR-15-16簇通过靶基因——成纤维细胞生长因子-2实现对抑制肿瘤的新生血管生成和远端转移的调控;临床相关性分析显示,miR-15-16簇的水平与结直肠癌患者的临床、病理特征密切相关,miR-15-16簇的表达水平能够作为潜在的标志物指示结直肠癌患者的预后；以上这些结果提示,肿瘤的缺氧微环境能够介导miR-15-16簇的表达下调,进而导致成纤维细胞生长因子-2失去转录后水平的抑制调控,从而达到促进肿瘤新生血管的生成以及肿瘤的远端转移的目的,我们的发现促进了人们对于肿瘤细胞在缺氧微环境中的应对机制的理解。综上所述,本研究为实体瘤缺氧微环境的深入理解以及实体瘤的早期诊断和靶向治疗提供了新的思路。
Hypoxia remains a major characteristic of solid tumors and defined but usually referring to tissues at oxygen levels below 5 to 10 mmHg. Malignant cell growth requires the presence of a local vascular network that supplies oxygen and nutrients. However, a highly proliferating mass of tumor cells develops faster than the vasculature, and tumor cells rapidly meet up with an avascular environment deficient in oxygen. Hypoxia affects a variety of tumor cell properties such as cell growth, apoptosis, neovascularization, metastasis and sensitivity to treatment. Therefore, how hypoxic environments are generated in tumor tissues and how cells respond to hypoxia are essential questions in understanding tumor progression and a better understanding of these processes may lead to novel strategies for diagnosis and treatment. microRNAs (miRNAs) are about 22 nucleotide RNA molecules that participate in a wide variety of physiological and pathological cellular processes such as cell differentiation, proliferation, death, metabolism and more recently tumorigenesis. Recent studies have established a link between a distinct miRNAs expression profile with hypoxia, and global miRNAs expression changes have been described to occur in human cancers and in some cases shown to correlate with the clinicopathological features of the tumor. However, there is still few mechanism has been proposed to date for these profile alterations and relatively little is known about miRNAs regulation and response to hypoxia.
In order to propose the mechanism of miRNAs response to hypoxia and involve in tumorigenesis or tumor progression, we screened the miRNA expression patterns in colorectal cancer (CRC) cell line cultured in diverse oxygen pressure using a high-resolution mapping assay, miRNA microarray and identified a specific group of hypoxia-related miRNAs with aberrant expression level. And then, the regulatory and acting mechanism of some important hypoxia-related miRNAs was investigated in vitro and in vivo. We found the expression levels of miR-17-92 cluster were reduced in hypoxia-treated cells containing wild-type p53, but were unchanged in hypoxia-treated p53-deficient cells. The repression of miR-17-92 cluster under hypoxia is independent of c-Myc, a promised transcription regulator of miR-17-92 cluster. Luciferase reporter assays mapped the region responding to p53-mediated repression to a p53-binding site in the proximal region of the miR-17-92 promoter. Chromatin immunoprecipitation (ChIP), Re-ChIP and gel retardation assays revealed that the binding sites for p53-and the TATA-binding protein (TBP)overlap within the promoter; these proteins were found to compete for binding. Over-express miR-17-92 cluster markedly inhibits hypoxia-induced apoptosis, whereas blocked miR-17-5p and miR-20a sensitize the cells to hypoxia-induced apoptosis. These data indicated that p53-mediated repression of miR-17-92 expression likely has an important function in hypoxia-induced apoptosis, and thus further our understanding of the tumor suppressive function of p53. Furthermore, we also demonstrate that the levels of miR-15-16 cluster are remarkably decreased under hypoxia and the low-expression favors colorectal cancer cell apoptosis, proliferative and especially invasive/metastatic behavior. Intratumoral administration of miRNAs shows that high levels of miR-15-16 cluster can significantly present angiogenesis and metastasis in a CRC nude mouse model, fibroblast growth factor-2 (FGF2), which regulates tissue angiogenesis, was identified as the direct and functional target of miR-15-16 both in vitro and in vivo. We also correlated the expression of miR-15-16 cluster with distant metastasis and clinical outcomes in malignant tissues. These data indicated that down-regulation of miR-15-16 cluster expression induced by hypoxia in CRC promotes tumor angiogenesis and distant metastasis by enhancement of FGF2 expression. In a word, our study provides a better understanding on the specificity of hypoxia and thus may be helpful in early diagnosis and targeting therapy of solid tumors
microRNAs (miRNAs)是一类长度约为22个核苷酸(nucleotide, nt)的非编码小分子RNA, miRNAs参与了包括细胞分化、增殖、代谢、死亡以及肿瘤生成等在内的一系列的细胞生理和病理进程。近年来大量的研究已经证实,miRNAs与肿瘤的缺氧微环境之间也存在着千丝万缕的联系。相比正常的组织,肿瘤组织中miRNAs的整体表达水平往往会发生巨大的改变,研究人员已经证实,在某些肿瘤中这种改变与肿瘤的临床、病理特征密切相关,但是直到今天,人们还未能对这种变化的意义做出确切的解释,miRNAs在肿瘤缺氧微环境中的调控和作用机制仍然有待于进一步的探索和发现。
为了探讨miRNAs与实体瘤缺氧微环境的相关性及其参与肿瘤发生、发展调控的具体机制,借助于高通量筛查手段——miRNAs芯片,我们对培养于不同氧浓度下的结直肠癌细胞系中miRNAs的表达情况进行检测和鉴定,筛选出了多种在缺氧状态下表达水平发生改变的miRNAs。在此基础之上,进一步通过体外、内实验对其中一些重要的缺氧相关miRNAs的调控和作用机制进行了深入的探讨。我们的研究显示,缺氧状态下培养的p53野生型细胞中miR-17-92簇的表达水平显著下调,而同样在缺氧状态下培养的p53突变型细胞中则没有变化,且这种缺氧依赖性的表达下调并不受已明确的miR-17-92簇转录调控因子c-Myc的控制；通过报告基因检测系统,我们发现miR-17-92簇启动子区的近端存在一个p53结合位点,通过与该位点的结合,p53在缺氧状态下对miR-17-92簇的表达水平进行抑制;免疫共沉淀、重复免疫共沉淀以及定量分析的结果显示,该位点与基本转录元件——TATA框重叠,p53与基本转录因子——TATA结合蛋白能够竞争性的结合于启动子上的这一区域;上调miR-17-92簇的表达能够明显抑制缺氧介导的细胞凋亡,而下调miR-17-92簇中主要成员miR-17-5p和miR-20a的表达会促进缺氧介导的细胞凋亡;以上这些结果都强烈提示,p53依赖性的miR-17-92簇表达下调在缺氧介导的细胞凋亡中发挥着重要的作用,因此我们的发现促进了人们对于p53的肿瘤抑制功能的理解。与此同时,我们还发现肿瘤的缺氧微环境能够导致miR-15-16簇的表达下调,进而影响肿瘤细胞的增殖、凋亡尤其是迁移和侵袭能力;通过结直肠癌原位动物模型,我们发现较高的miR-15-16簇表达水平能够抑制肿瘤的新生血管生成和远端转移(主要是肝转移);进一步的体外、内实验显示,miR-15-16簇通过靶基因——成纤维细胞生长因子-2实现对抑制肿瘤的新生血管生成和远端转移的调控;临床相关性分析显示,miR-15-16簇的水平与结直肠癌患者的临床、病理特征密切相关,miR-15-16簇的表达水平能够作为潜在的标志物指示结直肠癌患者的预后；以上这些结果提示,肿瘤的缺氧微环境能够介导miR-15-16簇的表达下调,进而导致成纤维细胞生长因子-2失去转录后水平的抑制调控,从而达到促进肿瘤新生血管的生成以及肿瘤的远端转移的目的,我们的发现促进了人们对于肿瘤细胞在缺氧微环境中的应对机制的理解。综上所述,本研究为实体瘤缺氧微环境的深入理解以及实体瘤的早期诊断和靶向治疗提供了新的思路。
Hypoxia remains a major characteristic of solid tumors and defined but usually referring to tissues at oxygen levels below 5 to 10 mmHg. Malignant cell growth requires the presence of a local vascular network that supplies oxygen and nutrients. However, a highly proliferating mass of tumor cells develops faster than the vasculature, and tumor cells rapidly meet up with an avascular environment deficient in oxygen. Hypoxia affects a variety of tumor cell properties such as cell growth, apoptosis, neovascularization, metastasis and sensitivity to treatment. Therefore, how hypoxic environments are generated in tumor tissues and how cells respond to hypoxia are essential questions in understanding tumor progression and a better understanding of these processes may lead to novel strategies for diagnosis and treatment. microRNAs (miRNAs) are about 22 nucleotide RNA molecules that participate in a wide variety of physiological and pathological cellular processes such as cell differentiation, proliferation, death, metabolism and more recently tumorigenesis. Recent studies have established a link between a distinct miRNAs expression profile with hypoxia, and global miRNAs expression changes have been described to occur in human cancers and in some cases shown to correlate with the clinicopathological features of the tumor. However, there is still few mechanism has been proposed to date for these profile alterations and relatively little is known about miRNAs regulation and response to hypoxia.
In order to propose the mechanism of miRNAs response to hypoxia and involve in tumorigenesis or tumor progression, we screened the miRNA expression patterns in colorectal cancer (CRC) cell line cultured in diverse oxygen pressure using a high-resolution mapping assay, miRNA microarray and identified a specific group of hypoxia-related miRNAs with aberrant expression level. And then, the regulatory and acting mechanism of some important hypoxia-related miRNAs was investigated in vitro and in vivo. We found the expression levels of miR-17-92 cluster were reduced in hypoxia-treated cells containing wild-type p53, but were unchanged in hypoxia-treated p53-deficient cells. The repression of miR-17-92 cluster under hypoxia is independent of c-Myc, a promised transcription regulator of miR-17-92 cluster. Luciferase reporter assays mapped the region responding to p53-mediated repression to a p53-binding site in the proximal region of the miR-17-92 promoter. Chromatin immunoprecipitation (ChIP), Re-ChIP and gel retardation assays revealed that the binding sites for p53-and the TATA-binding protein (TBP)overlap within the promoter; these proteins were found to compete for binding. Over-express miR-17-92 cluster markedly inhibits hypoxia-induced apoptosis, whereas blocked miR-17-5p and miR-20a sensitize the cells to hypoxia-induced apoptosis. These data indicated that p53-mediated repression of miR-17-92 expression likely has an important function in hypoxia-induced apoptosis, and thus further our understanding of the tumor suppressive function of p53. Furthermore, we also demonstrate that the levels of miR-15-16 cluster are remarkably decreased under hypoxia and the low-expression favors colorectal cancer cell apoptosis, proliferative and especially invasive/metastatic behavior. Intratumoral administration of miRNAs shows that high levels of miR-15-16 cluster can significantly present angiogenesis and metastasis in a CRC nude mouse model, fibroblast growth factor-2 (FGF2), which regulates tissue angiogenesis, was identified as the direct and functional target of miR-15-16 both in vitro and in vivo. We also correlated the expression of miR-15-16 cluster with distant metastasis and clinical outcomes in malignant tissues. These data indicated that down-regulation of miR-15-16 cluster expression induced by hypoxia in CRC promotes tumor angiogenesis and distant metastasis by enhancement of FGF2 expression. In a word, our study provides a better understanding on the specificity of hypoxia and thus may be helpful in early diagnosis and targeting therapy of solid tumors
引文
[1]Bristow RG, Hill RP. Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer.2008 Mar; 8(3):180-192.
[2]Michieli P. Hypoxia, angiogenesis and cancer therapy:to breathe or not to breathe? Cell Cycle.2009 Oct 15; 8(20):3291-3296
[3]Ruan K, Song G, Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem.2009 Aug 15; 107(6):1053-1062.
[4]Rademakers SE, Span PN, Kaanders JH, Sweep FC, van der Kogel AJ, Bussink J. Molecular aspects of tumour hypoxia. Mol Oncol.2008 Jun; 2(1):41-53.
[5]Trang P, Weidhaas JB, Slack FJ. MicroRNAs as potential cancer therapeutics. Oncogene.2008 Dec; 27 Suppl 2:S52-57.
[6]Shenouda SK, Alahari SK. MicroRNA function in cancer:oncogene or a tumor suppressor? Cancer Metastasis Rev.2009 Dec; 28(3-4):369-378.
[7]Zhang H, Li Y, Lai M. The microRNA network and tumor metastasis. Oncogene.2010 Feb 18; 29(7): 937-948.
[8]Slaby O, Svoboda M, Michalek J, Vyzula R. MicroRNAs in colorectal cancer:translation of molecular biology into clinical application. Mol Cancer.2009 Nov 14; 8:102.
[9]Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ, Davuluri R, Liu CG, Croce CM, Negrini M, Calin GA, Ivan M. A microRNA signature of hypoxia. Mol Cell Biol.2007 Mar; 27(5):1859-67.
[10]Kulshreshtha R, Davuluri RV, Calin GA, Ivan M. A microRNA component of the hypoxic response. Cell Death Differ.2008 Apr; 15(4):667-671.
[11]Ivan M, Harris AL, Martelli F, Kulshreshtha R. Hypoxia response and microRNAs:no longer two separate worlds. J Cell Mol Med.2008 Sep-Oct; 12(5A):1426-1431.
[12]Crosby ME, Devlin CM, Glazer PM, Calin GA, Ivan M. Emerging roles of microRNAs in the molecular responses to hypoxia. Curr Pharm Des.2009; 15(33):3861-3866.
[13]Dore LC, Amigo JD, Dos Santos CO, Zhang Z, Gai X, Tobias JW, Yu D, Klein AM, Dorman C, Wu W, Hardison RC, Paw BH, Weiss MJ. A GATA-1-regulated microRNA locus essential for erythropoiesis. Proc Natl Acad Sci U S A.2008 Mar 4; 105(9):3333-3338.
[14]Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res.2005 Nov 27; 33(20):e179.
[15]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods.2001 Dec; 25(4):402-408.
[16]Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A.2004 Jun 29; 101(26): 9740-9744.
[17]Lawrie CH, Soneji S, Marafioti T, Cooper CD, Palazzo S, Paterson JC, Cattan H, Enver T, Mager R, Boultwood J, Wainscoat JS, Hatton CS. MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer.2007 Sep 1; 121(5):1156-1161.
[18]Willenbrock H, Salomon J, Sokilde R, Barken KB, Hansen TN, Nielsen FC, Moller S, Litman T. Quantitative miRNA expression analysis:comparing microarrays with next-generation sequencing. RNA.2009 Nov; 15(11):2028-2034.
[19]Karczewski JM, Vet JA, Hessels D, Noordhoek J. p53-independent apoptosis induced by menadione in the human colon carcinoma cell line Caco-2. Ann N Y Acad Sci.2000; 915:275-278.
[20]Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell.2008 Apr 18; 133(2):217-222.
[21]van Haaften G, Agami R. Tumorigenicity of the miR-17-92 cluster distilled. Genes Dev.2010 Jan 1; 24(1):1-4.
[22]Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ. Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell. 2009 Sep 24; 35(6):856-867.
[23]Fasanaro P, Greco S, Lorenzi M, Pescatori M, Brioschi M, Kulshreshtha R, Banfi C, Stubbs A, Calin GA, Ivan M, Capogrossi MC, Martelli F. An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem.2009 Dec 11;284(50):35134-43.
[24]Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med.2008 Nov; 14(11):1271-1277.
[25]Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer:discovery, function and future perspectives. Cell Death Differ.2010 Feb; 17(2):215-220.
[1]Alarcon RM, Denko NC, Giaccia AJ. Genetic determinants that influence hypoxia-induced apoptosis. Novartis Found Symp.2001; 240:115-128.
[2]Bunz F, Hwang PM, Torrance C, Waldman T, Zhang Y, Dillehay L, Williams J, Lengauer C, Kinzler KW, Vogelstein B. Disruption of p53 in human cancer cells alters the responses to therapeutic agents. J Clin Invest.1999 Aug; 104(3):263-269.
[3]Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature.1996 Jan 4; 379(6560): 88-91.
[4]Harris AL. Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer.2002 Jan; 2(1):38-47.
[5]Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med.2005 Oct 27; 353(17):1793-17801.
[6]Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell.2004 Jan 23; 116(2): 281-297.
[7]Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell'Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A.2004 Aug 10; 101(32):11755-11760.
[8]Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res.2005 Nov 1; 65(21):9628-9632.
[9]Djelloul S, Forgue-Lafitte ME, Hermelin B, Mareel M, Bruyneel E, Baldi A, Giordano A, Chastre E, Gespach C. Enterocyte differentiation is compatible with SV40 large T expression and loss of p53 function in human colonic Caco-2 cells. Status of the pRbl and pRb2 tumor suppressor gene products. FEBS Lett.1997 Apr 14; 406(3):234-242.
[10]Cheng AM, Byrom MW, Shelton J, Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res.2005 Mar 1; 33(4): 1290-1297.
[11]Allegra CJ, Paik S, Colangelo LH, Parr AL, Kirsch I, Kim G, Klein P, Johnston PG, Wolmark N, Wieand HS. Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes'B and C colon cancer:a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study. J Clin Oncol.2003 Jan 15; 21(2):241-250.
[12]Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res.1994 Sep 15; 54(18):4855-4878.
[13]Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J. hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res.2008 Mar 1; 14(5):1340-1348.
[14]el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B. Definition of a consensus binding site for p53. Nat Genet.1992 Apr; 1(1):45-49.
[15]Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet.2006 Sep; 38(9):1060-1065.
[16]Fink T, Lund P, Pilgaard L, Rasmussen JG, Duroux M, Zachar V. Instability of standard PCR reference genes in adipose-derived stem cells during propagation, differentiation and hypoxic exposure. BMC Mol Biol.2008 Oct 31;9:98.
[17]Fontana L, Fiori ME, Albini S, Cifaldi L, Giovinazzi S, Forloni M, Boldrini R, Donfrancesco A, Federici V, Giacomini P, Peschle C, Fruci D. Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. PLoS One.2008 May 21; 3(5):e2236.
[18]Geisberg JV, Struhl K. Quantitative sequential chromatin immunoprecipitation, a method for analyzing co-occupancy of proteins at genomic regions in vivo. Nucleic Acids Res.2004 Nov 1; 32(19):e151.
[19]Hammond EM, Giaccia AJ. The role of p53 in hypoxia-induced apoptosis. Biochem Biophys Res Commun.2005 Jun 10; 331(3):718-725.
[20]Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell.2003 Dec 26; 115(7):787-798.
[21]He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. A microRNA polycistron as a potential human oncogene. Nature.2005 Jun 9; 435(7043):828-833.
[22]Hoffman WH, Biade S, Zilfou JT, Chen J, Murphy M. Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem.2002 Feb 1; 277(5):3247-3257.
[23]Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, Yamada H, Suzuki M, Nagino M, Nimura Y, Osada H, Takahashi T. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene.2007 Sep 6; 26(41): 6099-6105.
[24]Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia:dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol.2001 Feb; 21(4):1297-1310.
[25]Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science.1991 Jul 5; 253(5015):49-53.
[26]Krieg AJ, Hammond EM, Giaccia AJ. Functional analysis of p53 binding under differential stresses. Mol Cell Biol.2006 Oct; 26(19):7030-7045.
[27]O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature.2005 Jun 9; 435(7043):839-843.
[28]Ho JS, Ma W, Mao DY, Benchimol S. p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol Cell Biol.2005 Sep; 25(17):7423-7431.
[29]Marinescu VD, Kohane IS, Riva A. MAPPER:a search engine for the computational identification of putative transcription factor binding sites in multiple genomes. BMC Bioinformatics.2005 Mar 30; 6: 79. (http://mapper.chip.org/mapper/mapper).
[30]Murphy M, Hinman A, Levine AJ. Wild-type p53 negatively regulates the expression of a microtubule-associated protein. Genes Dev.1996 Dec 1; 10(23):2971-2980.
[31]Liu T, Laurell C, Selivanova G, Lundeberg J, Nilsson P, Wiman KG. Hypoxia induces p53-dependent transactivation and Fas/CD95-dependent apoptosis. Cell Death Differ.2007 Mar; 14(3):411-421.
[32]Ho JS, Ma W, Mao DY, Benchimol S. p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol Cell Biol.2005 Sep; 25(17):7423-7431.
[33]Ho J, Benchimol S. Transcriptional repression mediated by the p53 tumour suppressor. Cell Death Differ.2003 Apr; 10(4):404-408.
[34]Loyant V, Jaffre A, Breton J, Baldi I, Vital A, Chapon F, Dutoit S, Lecluse Y, Loiseau H, Lebailly P, Gauduchon P. Screening of TP53 mutations by DHPLC and sequencing in brain tumours from patients with an occupational exposure to pesticides or organic solvents. Mutagenesis.2005 Sep; 20(5):365-73.
[35]Chiou SK, Rao L, White E. Bcl-2 blocks p53-dependent apoptosis. Mol Cell Biol.1994 Apr; 14(4): 2556-2563.
[36]Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN. MicroRNA genes are transcribed by RNA polymerase Ⅱ. EMBO J.2004 Oct 13; 23(20):4051-60.
[37]Aguda BD, Kim Y, Piper-Hunter MG, Friedman A, Marsh CB. MicroRNA regulation of a cancer network:consequences of the feedback loops involving miR-17-92, E2F, and Myc. Proc Natl Acad Sci U S A.2008 Dec 16; 105(50):19678-19683.
[38]Coller HA, Forman JJ, Legesse-Miller A. "Myc'ed messages":myc induces transcription of E2F1 while inhibiting its translation via a microRNA polycistron. PLoS Genet.2007 Aug; 3(8):e146.
[39]Saikumar P, Dong Z, Patel Y, Hall K, Hopfer U, Weinberg JM, Venkatachalam MA. Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene.1998 Dec 31; 17(26):3401-15.
[40]Stempien-Otero A, Karsan A, Cornejo CJ, Xiang H, Eunson T, Morrison RS, Kay M, Winn R, Harlan J. Mechanisms of hypoxia-induced endothelial cell death. Role of p53 in apoptosis. J Biol Chem.1999 Mar 19; 274(12):8039-8045.
[41]Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A, Dannenberg AJ. Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem.1999 Apr 16; 274(16):10911-10915.
[42]Takakura S, Mitsutake N, Nakashima M, Namba H, Saenko VA, Rogounovitch TI, Nakazawa Y, Hayashi T, Ohtsuru A, Yamashita S. Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci.2008 Jun; 99(6):1147-1154.
[43]Tanzer A, Stadler PF. Molecular evolution of a microRNA cluster. J Mol Biol.2004 May 28; 339(2): 327-335.
[44]Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A.2006 Feb 14; 103(7):2257-2261.
[45]Wang L, Wu Q, Qiu P, Mirza A, McGuirk M, Kirschmeier P, Greene JR, Wang Y, Pickett CB, Liu S. Analyses of p53 target genes in the human genome by bioinformatic and microarray approaches. J Biol Chem.2001 Nov 23; 276(47):43604-43610.
[46]Weinmann M, Jendrossek V, Guner D, Goecke B, Belka C. Cyclic exposure to hypoxia and reoxygenation selects for tumor cells with defects in mitochondrial apoptotic pathways. FASEB J.2004 Dec; 18(15):1906-1908.
[47]Woods K, Thomson JM, Hammond SM. Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. J Biol Chem.2007 Jan 26; 282(4):2130-2134.
[48]Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol.2008 Apr;9(4):405-414.
[49]Yu J, Wang Z, Kinzler KW, Vogelstein B, Zhang L. PUMA mediates the apoptotic response to p53 in colorectal cancer cells. Proc Natl Acad Sci U S A.2003 Feb 18; 100(4):1931-1936.
[1]Kahi CJ, Rex DK, Imperiale TF. Screening, surveillance, and primary prevention for colorectal cancer: a review of the recent literature. Gastroenterology.2008 Aug; 135(2):380-399.
[2]Wolpin BM, Meyerhardt JA, Mamon HJ, Mayer RJ. Adjuvant treatment of colorectal cancer. CA Cancer J Clin.2007 May-Jun; 57(3):168-185.
[3]Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009 Nov-Dec; 59(6):366-78.
[4]Carpizo DR, D'Angelica M. Liver resection for metastatic colorectal cancer in the presence of extrahepatic disease. Lancet Oncol.2009 Aug; 10(8):801-809.
[5]Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol.2009 Nov 1; 27(31):5287-5297.
[6]Bessette DC, Qiu D, Pallen CJ. PRL PTPs:mediators and markers of cancer progression. Cancer Metastasis Rev.2008 Jun; 27(2):231-252.
[7]Hill RP, Marie-Egyptienne DT, Hedley DW. Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol.2009 Apr; 19(2):106-111.
[8]Nannini M, Pantaleo MA, Maleddu A, Astolfi A, Formica S, Biasco G. Gene expression profiling in colorectal cancer using microarray technologies:results and perspectives. Cancer Treat Rev.2009 May; 35(3):201-209. Epub 2008 Dec 9.
[9]Bristow RG, Hill RP. Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer.2008 Mar; 8(3):180-192.
[10]Horan AD, Koch CJ. The K(m) for Radiosensitization of Human Tumor Cells by Oxygen is Much Greater than 3 mmHg and is Further Increased by Elevated Levels of Cysteine. Radiat Res.2001 Oct; 156(4):388-398.
[11]Stockmann C, Doedens A, Weidemann A, Zhang N, Takeda N, Greenberg JI, Cheresh DA, Johnson RS. Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature.2008 Dec 11; 456(7223):814-818.
[12]Bertout JA, Patel SA, Simon MC. The impact of 02 availability on human cancer. Nat Rev Cancer. 2008 Dec; 8(12):967-975.
[13]Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer.2008 Jun; 8(6):425-437.
[14]Chaudary N, Hill RP. Hypoxia and metastasis. Clin Cancer Res.2007 Apr 1; 13(7):1947-1949.
[15]Ruan K, Song G, Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem.2009 Aug 15; 107(6):1053-1062.
[16]Chan DA, Giaccia AJ. Hypoxia, gene expression, and metastasis. Cancer Metastasis Rev.2007 Jun; 26(2):333-339.
[17]Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet.2009 Oct; 10(10):704-714.
[18]Mott JL. MicroRNAs involved in tumor suppressor and oncogene pathways:implications for hepatobiliary neoplasia. Hepatology.2009 Aug; 50(2):630-637.
[19]Segura MF, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S, Zakrzewski J, Blochin E, Rose A, Bogunovic D, Polsky D, Wei J, Lee P, Belitskaya-Levy I, Bhardwaj N, Osman I, Hernando E. Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci U S A.2009 Feb 10; 106(6): 1814-1819.
[20]Kulshreshtha R, Davuluri RV, Calin GA, Ivan M. A microRNA component of the hypoxic response. Cell Death Differ.2008 Apr; 15(4):667-671.
[21]Ivan M, Harris AL, Martelli F, Kulshreshtha R. Hypoxia response and microRNAs:no longer two separate worlds. J Cell Mol Med.2008 Sep-Oct; 12(5A):1426-1431.
[22]Mallick B, Ghosh Z, Chakrabarti J. MicroRNome analysis unravels the molecular basis of SARS infection in bronchoalveolar stem cells. PLoS One.2009 Nov 13; 4(11):e7837.
[23]Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity:microRNA biogenesis pathways and their regulation. Nat Cell Biol.2009 Mar; 11(3):228-234.
[24]Dore LC, Amigo JD, Dos Santos CO, Zhang Z, Gai X, Tobias JW, Yu D, Klein AM, Dorman C, Wu W, Hardison RC, Paw BH, Weiss MJ. A GATA-1-regulated microRNA locus essential for erythropoiesis. Proc Natl Acad Sci U S A.2008 Mar 4; 105(9):3333-3338.
[25]Sambrook J,Russell DW. Molecular Cloning:A Laboratory Manual (Third Edition).Cold Spring Harbor Laboratory Press,2001.
[26]Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature.2007 Oct 11; 449(7163):682-688.
[27]Zhu X, Asa SL, Ezzat S. Fibroblast growth factor 2 and estrogen control the balance of histone 3 modifications targeting MAGE-A3 in pituitary neoplasia. Clin Cancer Res.2008 Apr 1; 14(7): 1984-1996.
[28]Behrens C, Lin HY, Lee JJ, Raso MG, Hong WK, Wistuba Ⅱ, Lotan R. Immunohistochemical expression of basic fibroblast growth factor and fibroblast growth factor receptors 1 and 2 in the pathogenesis of lung cancer. Clin Cancer Res.2008 Oct 1; 14(19):6014-6022.
[29]Fromowitz FB, Viola MV, Chao S, Oravez S, Mishriki Y, Finkel G, Grimson R, Lundy J. ras p21 expression in the progression of breast cancer. Hum Pathol.1987 Dec; 18(12):1268-1275.
[30]Banning A, Kipp A, Schmitmeier S, Lowinger M, Florian S, Krehl S, Thalmann S, Thierbach R, Steinberg P, Brigelius-Flohe R. Glutathione Peroxidase 2 Inhibits Cyclooxygenase-2-Mediated Migration and Invasion of HT-29 Adenocarcinoma Cells but Supports Their Growth as Tumors in Nude Mice. Cancer Res.2008 Dec 1; 68(23):9746-9753.
[31]Lendahl U, Lee KL, Yang H, Poellinger L. Generating specificity and diversity in the transcriptional response to hypoxia. Nat Rev Genet.2009 Dec; 10(12):821-832.
[32]Yan HL, Xue G, Mei Q, Wang YZ, Ding FX, Liu MF, Lu MH, Tang Y, Yu HY, Sun SH. Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J.2009 Sep 16; 28(18):2719-2732.
[33]Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ. Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell. 2009 Sep 24; 35(6):856-867.
[34]Hebert C, Norris K, Scheper MA, Nikitakis N, Sauk JJ. High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol Cancer.2007 Jan 14; 6:5.
[35]Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med.2008 Nov; 14(11):1271-1277.
[36]Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC. miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol.2005 Jul; 204(1):280-285.
[37]Hanlon K, Rudin CE, Harries LW. Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL). PLoS One.2009 Sep 25; 4(9):e7169.
[38]Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A.2005 Sep 27; 102(39):13944-13949.
[39]Cao Y, Cao R, Hedlund EM. R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways. J Mol Med.2008 Jul; 86(7):785-789. Epub 2008 Apr 8.
[40]Katoh M, Katoh M. FGF signaling network in the gastrointestinal tract (review). Int J Oncol.2006 Jul; 29(1):163-168.
[41]Katoh M. Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. Stem Cell Rev.2007 Jan; 3(1):30-38.
[42]Katoh Y, Katoh M. FGF signaling inhibitor, SPRY4, is evolutionarily conserved target of WNT signaling pathway in progenitor cells. Int J Mol Med.2006 Mar; 17(3):529-532.
[1]Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell.1993 Dec 3; 75(5):843-854.
[2]Carrington JC, Ambros V. Role of microRNAs in plant and animal development. Science.2003 Jul 18; 301(5631):336-338.
[3]Griffiths-Jones S. The microRNA Registry. Nucleic Acids Res.2004 Jan 1; 32(Database issue): D109-111.
[4]Kim HH, Kuwano Y, Srikantan S, Lee EK, Martindale JL, Gorospe M. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev.2009 Aug 1; 23(15):1743-1748.
[5]Zhang C. Novel functions for small RNA molecules. Curr Opin Mol Ther.2009 Dec; 11(6):641-651.
[6]Tang JT, Fang JY. MicroRNA regulatory network in human colorectal cancer. Mini Rev Med Chem. 2009 Jul; 9(8):921-926.
[7]Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A.2004 Mar 2; 101(9):2999-3004.
[8]Li SC, Tang P, Lin WC. Intronic microRNA:discovery and biological implications. DNA Cell Biol. 2007 Apr; 26(4):195-207.
[9]Miyoshi K, Okada TN, Siomi H, Siomi MC. Characterization of the miRNA-RISC loading complex and miRNA-RISC formed in the Drosophila miRNA pathway. RNA.2009 Jul; 15(7):1282-1291.
[10]Kawamata T, Seitz H, Tomari Y. Structural determinants of miRNAs for RISC loading and slicer-independent unwinding. Nat Struct Mol Biol.2009 Sep; 16(9):953-960.
[11]Berezikov E, Liu N, Flynt AS, Hodges E, Rooks M, Hannon GJ, Lai EC. Evolutionary flux of canonical microRNAs and mirtrons in Drosophila. Nat Genet.2010 Jan; 42(1):6-9.
[12]Berezikov E, Chung WJ, Willis J, Cuppen E, Lai EC. Mammalian mirtron genes. Mol Cell.2007 Oct 26; 28(2):328-336.
[13]Sevignani C, Calin GA, Siracusa LD, Croce CM. Mammalian microRNAs:a small world for fine-tuning gene expression. Mamm Genome.2006 Mar; 17(3):189-202.
[14]Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell.2005 Nov 18; 123(4):631-640.
[15]Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol.2002 Apr 30; 12(9):735-739.
[16]Houbaviy HB, Murray MF, Sharp PA. Embryonic stem cell-specific MicroRNAs. Dev Cell.2003 Aug; 5(2):351-358.
[17]Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science.2004 Jan 2; 303(5654):83-86.
[18]Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science.2001 Oct 26; 294(5543):853-858.
[19]Kai ZS, Pasquinelli AE. MicroRNA assassins:factors that regulate the disappearance of miRNAs. Nat Struct Mol Biol.2010 Jan; 17(1):5-10.
[20]Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A.2006 Mar 14; 103(11):4034-4039.
[21]Zhang H, Li Y, Lai M. The microRNA network and tumor metastasis. Oncogene.2010 Feb 18; 29(7): 937-948.
[22]Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell.2004 Jan 23; 116(2): 281-297.
[23]Kolb FA, Zhang H, Jaronczyk K, Tahbaz N, Hobman TC, Filipowicz W. Human dicer:purification, properties, and interaction with PAZ PIWI domain proteins. Methods Enzymol.2005; 392:316-336.
[24]Zhang B, Pan X. Expression of microRNAs in cotton. Mol Biotechnol.2009 Jul; 42(3):269-274.
[25]Kutter C, Svoboda P. miRNA, siRNA, piRNA:Knowns of the unknown. RNA Biol.2008 Oct-Dec; 5(4):181-188.
[26]Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol.1999 Dec 15; 216(2):671-680.
[27]Steitz JA, Vasudevan S. miRNPs:versatile regulators of gene expression in vertebrate cells. Biochem Soc Trans.2009 Oct; 37(Pt 5):931-935.
[28]Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J, Di Padova F, Lin SC, Gram H; Han J. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell.2005 Mar 11; 120(5):623-634.
[29]Carthew RW, Sontheimer EJ. Origins and Mechanisms of miRNAs and siRNAs. Cell.2009 Feb 20; 136(4):642-655.
[30]Huang J, Hao P, Chen H, Hu W, Yan Q, Liu F, Han ZG. Genome-wide identification of Schistosoma japonicum microRNAs using a deep-sequencing approach. PLoS One.2009 Dec 8; 4(12):e8206.
[31]Joshi T, Yan Z, Libault M, Jeong DH, Park S, Green PJ, Sherrier DJ, Farmer A, May G, Meyers BC, Xu D, Stacey G. Prediction of novel miRNAs and associated target genes in Glycine max. BMC Bioinformatics.2010 Jan 18; 11 Suppl 1:S14.
[32]Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science.2001 Oct 26; 294(5543):862-864.
[33]Michael MZ. Cloning microRNAs from mammalian tissues. Methods Mol Biol.2006; 342:189-207.
[34]Hafner M, Landgraf P, Ludwig J, Rice A, Ojo T, Lin C, Holoch D, Lim C, Tuschl T. Identification of microRNAs and other small regulatory RNAs using cDNA library sequencing. Methods.2008 Jan; 44(1):3-12.
[35]Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, Cha KY, Chung HM, Yoon HS, Moon SY, Kim VN, Kim KS. Human embryonic stem cells express a unique set of microRNAs. Dev Biol.2004 Jun 15; 270(2):488-498.
[36]Yoon S, De Micheli G. Computational identification of microRNAs and their targets. Birth Defects Res C Embryo Today.2006 Jun; 78(2):118-128.
[37]Lim LP, Lau NC, Weinstein EG, Abdelhakim A, Yekta S, Rhoades MW, Burge CB, Bartel DP. The microRNAs of Caenorhabditis elegans. Genes Dev.2003 Apr 15; 17(8):991-1008.
[38]Grad Y, Aach J, Hayes GD, Reinhart BJ, Church GM, Ruvkun G, Kim J. Computational and experimental identification of C. elegans microRNAs. Mol Cell.2003 May; 11(5):1253-63.
[39]Zhang BH, Pan XP, Cox SB, Cobb GP, Anderson TA. Evidence that miRNAs are different from other RNAs. Cell Mol Life Sci.2006 Jan; 63(2):246-254.
[40]Bentwich I. Prediction and validation of microRNAs and their targets. FEBS Lett.2005 Oct 31; 579(26):5904-5910.
[41]Watanabe Y, Tomita M, Kanai A. Computational methods for microRNA target prediction. Methods Enzymol.2007; 427:65-86.
[42]Stark A, Brennecke J, Russell RB, Cohen SM. Identification of Drosophila MicroRNA targets. PLoS Biol.2003 Dec; 1(3):E60.
[43]John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA targets. PLoS Biol. 2004 Nov; 2(11):e363.
[44]Xia W, Cao G, Shao N. Progress in miRNA target prediction and identification. Sci China C Life Sci. 2009 Dec; 52(12):1123-1130.
[45]Wark AW, Lee HJ, Corn RM. Multiplexed detection methods for profiling microRNA expression in biological samples. Angew Chem Int Ed Engl.2008; 47(4):644-652.
[46][15] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods.2001 Dec; 25(4):402-408.
[47]Bandres E, Cubedo E, Agirre X, Malumbres R, Zarate R, Ramirez N, Abajo A, Navarro A, Moreno 1, Monzo M, Garcia-Foncillas J. Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer.2006 Jul 19; 5:29.
[48]Lao K, Xu NL, Yeung V, Chen C, Livak KJ, Straus NA. Multiplexing RT-PCR for the detection of multiple miRNA species in small samples. Biochem Biophys Res Commun.2006 Apr 28; 343(1): 85-89.
[49]Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A.2004 Jun 29; 101(26):9740-9744.
[50]Li W, Ruan K. MicroRNA detection by microarray. Anal Bioanal Chem.2009 Jun; 394(4): 1117-1124.
[51]Yamayoshi A, Momokawa D, Kobori A, Murakami A. Development of peptide-oligonucleotide conjugates for regulation of small RNA function. Nucleic Acids Symp Ser (Oxf).2009; (53):53-54.
[52]Orom UA, Lund AH. Isolation of microRNA targets using biotinylated synthetic microRNAs. Methods.2007 Oct; 43(2):162-165.
[53]Marquez RT, McCaffrey AP. Advances in microRNAs:implications for gene therapists. Hum Gene Ther.2008 Jan; 19(1):27-38.
[54]Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, Bozzoni I. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell.2005 Dec 2; 123(5):819-831.
[55]Wang B, Doench JG, Novina CD. Analysis of microRNA effector functions in vitro. Methods.2007 Oct; 43(2):91-104.
[56]Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science.2004 Apr 23; 304(5670):594-596.
[57]Cowland JB, Hother C, Grenbaek K. MicroRNAs and cancer. APMIS.2007 Oct; 115(10): 1090-1106.
[58]Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet.2007 May; 39(5):673-677.
[59]Voorhoeve PM. MicroRNAs:Oncogenes, tumor suppressors or master regulators of cancer heterogeneity? Biochim Biophys Acta.2010 Jan; 1805(1):72-86.
[60]Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell.2008 Apr 18; 133(2):217-222.
[61]Ernst A, Campos B, Meier J, Devens F, Liesenberg F, Wolter M, Reifenberger G, Herold-Mende C, Lichter P, Radlwimmer B. De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures. Oncogene.2010 Mar 22. [Epub ahead of print]
[62]Aguda BD, Kim Y, Piper-Hunter MG, Friedman A, Marsh CB. MicroRNA regulation of a cancer network:consequences of the feedback loops involving miR-17-92, E2F, and Myc. Proc Natl Acad Sci U S A.2008 Dec 16; 105(50):19678-19683.
[63]Yan HL, Xue G, Mei Q, Wang YZ, Ding FX, Liu MF, Lu MH, Tang Y, Yu HY, Sun SH. Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J. 2009 Sep 16; 28(18):2719-2732.
[64]Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun.2005 Sep 9; 334(4):1351-1358.
[65]Qi L, Bart J, Tan LP, Platteel I, Sluis T, Huitema S, Harms Q Fu L, Hollema H, Berg A. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma. BMC Cancer.2009 May 28; 9:163.
[66]Krichevsky AM, Gabriely G. miR-21:a small multi-faceted RNA. J Cell Mol Med.2009 Jan;13(1):39-53.
[67]Loffler D, Brocke-Heidrich K, Pfeifer G, Stocsits C, Hackermuller J, Kretzschmar AK, Burger R, Gramatzki M, Blumert C, Bauer K, Cvijic H, Ullmann AK, Stadler PF, Horn F. Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood.2007 Aug 15; 110(4):1330-1333.
[68]Tili E, Croce CM, Michaille JJ. miR-155:on the crosstalk between inflammation and cancer. Int Rev Immunol.2009; 28(5):264-284.
|69] Kluiver J, Haralambieva E, de Jong D, Blokzijl T, Jacobs S, Kroesen BJ, Poppema S, van den Berg A. Lack of BIC and microRNA miR-155 expression in primary cases of Burkitt lymphoma. Genes Chromosomes Cancer.2006 Feb; 45(2):147-153.
[70]Roush S, Slack FJ. The let-7 family of microRNAs. Trends Cell Biol.2008 Oct; 18(10):505-516.
[71]Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ. RAS is regulated by the let-7 microRNA family. Cell.2005 Mar 11; 120(5): 635-647.
[72]Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res.2004 Jun 1; 64(11): 3753-3756.
[73]Boyerinas B, Park SM, Shomron N, Hedegaard MM, Vinther J, Andersen JS, Feig C, Xu J, Burge CB, Peter ME. Identification of let-7-regulated oncofetal genes. Cancer Res.2008 Apr 15; 68(8): 2587-2591.
[74]Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer:discovery, function and future perspectives. Cell Death Differ.2010 Feb; 17(2):215-220.
[75]Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A.2008 Apr 1; 105(13):5166-5171.
[76]Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC. miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol.2005 Jul; 204(1):280-285.
[77]Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A.2005 Sep 27; 102(39): 13944-13949.
[78]Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med.2008 Nov; 14(11):1271-1277.
[79]Bartels CL, Tsongalis GJ. MicroRNAs:novel biomarkers for human cancer. Clin Chem.2009 Apr; 55(4):623-631.
[80]Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, Morgan DL, Postier RG, Brackett DJ, Schmittgen TD. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer.2007 Mar 1; 120(5):1046-1054.
[81]Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature.2005 Jun 9; 435(7043):834-838.
[82]Bottoni A, Zatelli MC, Ferracin M, Tagliati F, Piccin D, Vignali C, Calin GA, Negrini M, Croce CM, Degli Uberti EC. Identification of differentially expressed microRNAs by microarray:a possible role for microRNA genes in pituitary adenomas. J Cell Physiol.2007 Feb; 210(2):370-377.
[83]Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell'Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A.2004 Aug 10; 101(32):11755-11760.
[84]Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, Calin GA, Volinia S, Liu CG, Scarpa A, Croce CM. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol.2006 Oct 10; 24(29):4677-4684.
[85]Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA.2007 May 2; 297(17):1901-1908.
[86]Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell.2006 Mar; 9(3):189-198.
[87]Trang P, Weidhaas JB, Slack FJ. MicroRNAs as potential cancer therapeutics. Oncogene.2008 Dec; 27 Suppl 2:S52-57.
[88]Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC. Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem. 2007 Jan 12; 282(2):1479-1486.
[89]Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with'antagomirs'. Nature.2005 Dec 1; 438(7068):685-9.
[90]Hummel R, Hussey DJ, Haier J. MicroRNAs:predictors and modifiers of chemo-and radiotherapy in different tumour types. Eur J Cancer.2010 Jan; 46(2):298-311.
[91]Li C, Feng Y, Coukos G, Zhang L. Therapeutic microRNA strategies in human cancer. AAPS J.2009 Dec; 11(4):747-757.
[92]Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P, Salazar F, Kay MA. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature. 2006 May 25; 441(7092):537-541.
[93]Stenvang J, Silahtaroglu AN, Lindow M, Elmen J, Kauppinen S. The utility of LNA in microRNA-based cancer diagnostics and therapeutics. Semin Cancer Biol.2008 Apr; 18(2):89-102.
[94]Grimm D, Kay MA. RNAi and gene therapy:a mutual attraction. Hematology Am Soc Hematol Educ Program.2007:473-481.
[95]Aagaard L, Rossi JJ. RNAi therapeutics:principles, prospects and challenges. Adv Drug Deliv Rev. 2007 Mar 30; 59(2-3):75-86.
[96]Wu X, Xiao H. miRNAs modulate the drug response of tumor cells. Sci China C Life Sci.2009 Sep; 52(9):797-801.
[97]Fojo T. Multiple paths to a drug resistance phenotype:mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs. Drug Resist Updat.2007 Feb-Apr; 10(1-2):59-67.
[98]Svoboda M, Izakovicova Holla L, Sefr R, Vrtkova I, Kocakova I, Tichy B, Dvorak J. Micro-RNAs miR125b and miR137 are frequently upregulated in response to capecitabine chemoradiotherapy of rectal cancer. Int J Oncol.2008 Sep; 33(3):541-547.
[99]Nasser MW, Datta J, Nuovo G, Kutay H, Motiwala T, Majumder S, Wang B, Suster S, Jacob ST, Ghoshal K. Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem.2008 Nov 28; 283(48):33394-33405.
[100]Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene.2007 Apr 26; 26(19):2799-2803.
[101]Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, Jiang J, Schmittgen TD, Patel T. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology.2006 Jun; 130(7):2113-2129.
[102]Rokhlin OW, Scheinker VS, Taghiyev AF, Bumcrot D, Glover RA, Cohen MB. MicroRNA-34 mediates AR-dependent p53-induced apoptosis in prostate cancer. Cancer Biol Ther.2008 Aug; 7(8): 1288-1296.
[103]Iorio MV, Croce CM. MicroRNAs in cancer:small molecules with a huge impact. J Clin Oncol.2009 Dec 1; 27(34):5848-5856.
[104]Weiss GJ, Bemis LT, Nakajima E, Sugita M, Birks DK, Robinson WA, Varella-Garcia M, Bunn PA Jr, Haney J, Helfrich BA, Kato H, Hirsch FR, Franklin WA. EGFR regulation by microRNA in lung cancer:correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. Ann Oncol.2008 Jun; 19(6):1053-1059.
[105]Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem. 2008 Oct 31; 283(44):29897-28903.
[106]Zhao JJ, Lin J, Yang H, Kong W, He L, Ma X, Coppola D, Cheng JQ. MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem.2008 Nov 7; 283(45):31079-31086.
[107]Thorburn A, Behbakht K, Ford H. TRAIL receptor-targeted therapeutics:resistance mechanisms and strategies to avoid them. Drug Resist Updat.2008 Feb-Apr; 11(1-2):17-24.
[108]Garofalo M, Quintavalle C, Di Leva G, Zanca C, Romano G, Taccioli C, Liu CG, Croce CM, Condorelli G. MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene.2008 Jun 19; 27(27):3845-3855.
[109]Corsten MF, Miranda R, Kasmieh R, Krichevsky AM, Weissleder R, Shah K. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res.2007 Oct 1; 67(19):8994-9000.
[2]Michieli P. Hypoxia, angiogenesis and cancer therapy:to breathe or not to breathe? Cell Cycle.2009 Oct 15; 8(20):3291-3296
[3]Ruan K, Song G, Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem.2009 Aug 15; 107(6):1053-1062.
[4]Rademakers SE, Span PN, Kaanders JH, Sweep FC, van der Kogel AJ, Bussink J. Molecular aspects of tumour hypoxia. Mol Oncol.2008 Jun; 2(1):41-53.
[5]Trang P, Weidhaas JB, Slack FJ. MicroRNAs as potential cancer therapeutics. Oncogene.2008 Dec; 27 Suppl 2:S52-57.
[6]Shenouda SK, Alahari SK. MicroRNA function in cancer:oncogene or a tumor suppressor? Cancer Metastasis Rev.2009 Dec; 28(3-4):369-378.
[7]Zhang H, Li Y, Lai M. The microRNA network and tumor metastasis. Oncogene.2010 Feb 18; 29(7): 937-948.
[8]Slaby O, Svoboda M, Michalek J, Vyzula R. MicroRNAs in colorectal cancer:translation of molecular biology into clinical application. Mol Cancer.2009 Nov 14; 8:102.
[9]Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ, Davuluri R, Liu CG, Croce CM, Negrini M, Calin GA, Ivan M. A microRNA signature of hypoxia. Mol Cell Biol.2007 Mar; 27(5):1859-67.
[10]Kulshreshtha R, Davuluri RV, Calin GA, Ivan M. A microRNA component of the hypoxic response. Cell Death Differ.2008 Apr; 15(4):667-671.
[11]Ivan M, Harris AL, Martelli F, Kulshreshtha R. Hypoxia response and microRNAs:no longer two separate worlds. J Cell Mol Med.2008 Sep-Oct; 12(5A):1426-1431.
[12]Crosby ME, Devlin CM, Glazer PM, Calin GA, Ivan M. Emerging roles of microRNAs in the molecular responses to hypoxia. Curr Pharm Des.2009; 15(33):3861-3866.
[13]Dore LC, Amigo JD, Dos Santos CO, Zhang Z, Gai X, Tobias JW, Yu D, Klein AM, Dorman C, Wu W, Hardison RC, Paw BH, Weiss MJ. A GATA-1-regulated microRNA locus essential for erythropoiesis. Proc Natl Acad Sci U S A.2008 Mar 4; 105(9):3333-3338.
[14]Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res.2005 Nov 27; 33(20):e179.
[15]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods.2001 Dec; 25(4):402-408.
[16]Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A.2004 Jun 29; 101(26): 9740-9744.
[17]Lawrie CH, Soneji S, Marafioti T, Cooper CD, Palazzo S, Paterson JC, Cattan H, Enver T, Mager R, Boultwood J, Wainscoat JS, Hatton CS. MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer.2007 Sep 1; 121(5):1156-1161.
[18]Willenbrock H, Salomon J, Sokilde R, Barken KB, Hansen TN, Nielsen FC, Moller S, Litman T. Quantitative miRNA expression analysis:comparing microarrays with next-generation sequencing. RNA.2009 Nov; 15(11):2028-2034.
[19]Karczewski JM, Vet JA, Hessels D, Noordhoek J. p53-independent apoptosis induced by menadione in the human colon carcinoma cell line Caco-2. Ann N Y Acad Sci.2000; 915:275-278.
[20]Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell.2008 Apr 18; 133(2):217-222.
[21]van Haaften G, Agami R. Tumorigenicity of the miR-17-92 cluster distilled. Genes Dev.2010 Jan 1; 24(1):1-4.
[22]Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ. Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell. 2009 Sep 24; 35(6):856-867.
[23]Fasanaro P, Greco S, Lorenzi M, Pescatori M, Brioschi M, Kulshreshtha R, Banfi C, Stubbs A, Calin GA, Ivan M, Capogrossi MC, Martelli F. An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem.2009 Dec 11;284(50):35134-43.
[24]Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med.2008 Nov; 14(11):1271-1277.
[25]Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer:discovery, function and future perspectives. Cell Death Differ.2010 Feb; 17(2):215-220.
[1]Alarcon RM, Denko NC, Giaccia AJ. Genetic determinants that influence hypoxia-induced apoptosis. Novartis Found Symp.2001; 240:115-128.
[2]Bunz F, Hwang PM, Torrance C, Waldman T, Zhang Y, Dillehay L, Williams J, Lengauer C, Kinzler KW, Vogelstein B. Disruption of p53 in human cancer cells alters the responses to therapeutic agents. J Clin Invest.1999 Aug; 104(3):263-269.
[3]Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature.1996 Jan 4; 379(6560): 88-91.
[4]Harris AL. Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer.2002 Jan; 2(1):38-47.
[5]Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med.2005 Oct 27; 353(17):1793-17801.
[6]Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell.2004 Jan 23; 116(2): 281-297.
[7]Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell'Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A.2004 Aug 10; 101(32):11755-11760.
[8]Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res.2005 Nov 1; 65(21):9628-9632.
[9]Djelloul S, Forgue-Lafitte ME, Hermelin B, Mareel M, Bruyneel E, Baldi A, Giordano A, Chastre E, Gespach C. Enterocyte differentiation is compatible with SV40 large T expression and loss of p53 function in human colonic Caco-2 cells. Status of the pRbl and pRb2 tumor suppressor gene products. FEBS Lett.1997 Apr 14; 406(3):234-242.
[10]Cheng AM, Byrom MW, Shelton J, Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res.2005 Mar 1; 33(4): 1290-1297.
[11]Allegra CJ, Paik S, Colangelo LH, Parr AL, Kirsch I, Kim G, Klein P, Johnston PG, Wolmark N, Wieand HS. Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes'B and C colon cancer:a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study. J Clin Oncol.2003 Jan 15; 21(2):241-250.
[12]Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res.1994 Sep 15; 54(18):4855-4878.
[13]Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J. hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res.2008 Mar 1; 14(5):1340-1348.
[14]el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B. Definition of a consensus binding site for p53. Nat Genet.1992 Apr; 1(1):45-49.
[15]Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet.2006 Sep; 38(9):1060-1065.
[16]Fink T, Lund P, Pilgaard L, Rasmussen JG, Duroux M, Zachar V. Instability of standard PCR reference genes in adipose-derived stem cells during propagation, differentiation and hypoxic exposure. BMC Mol Biol.2008 Oct 31;9:98.
[17]Fontana L, Fiori ME, Albini S, Cifaldi L, Giovinazzi S, Forloni M, Boldrini R, Donfrancesco A, Federici V, Giacomini P, Peschle C, Fruci D. Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. PLoS One.2008 May 21; 3(5):e2236.
[18]Geisberg JV, Struhl K. Quantitative sequential chromatin immunoprecipitation, a method for analyzing co-occupancy of proteins at genomic regions in vivo. Nucleic Acids Res.2004 Nov 1; 32(19):e151.
[19]Hammond EM, Giaccia AJ. The role of p53 in hypoxia-induced apoptosis. Biochem Biophys Res Commun.2005 Jun 10; 331(3):718-725.
[20]Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell.2003 Dec 26; 115(7):787-798.
[21]He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. A microRNA polycistron as a potential human oncogene. Nature.2005 Jun 9; 435(7043):828-833.
[22]Hoffman WH, Biade S, Zilfou JT, Chen J, Murphy M. Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem.2002 Feb 1; 277(5):3247-3257.
[23]Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, Yamada H, Suzuki M, Nagino M, Nimura Y, Osada H, Takahashi T. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene.2007 Sep 6; 26(41): 6099-6105.
[24]Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia:dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol.2001 Feb; 21(4):1297-1310.
[25]Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science.1991 Jul 5; 253(5015):49-53.
[26]Krieg AJ, Hammond EM, Giaccia AJ. Functional analysis of p53 binding under differential stresses. Mol Cell Biol.2006 Oct; 26(19):7030-7045.
[27]O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature.2005 Jun 9; 435(7043):839-843.
[28]Ho JS, Ma W, Mao DY, Benchimol S. p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol Cell Biol.2005 Sep; 25(17):7423-7431.
[29]Marinescu VD, Kohane IS, Riva A. MAPPER:a search engine for the computational identification of putative transcription factor binding sites in multiple genomes. BMC Bioinformatics.2005 Mar 30; 6: 79. (http://mapper.chip.org/mapper/mapper).
[30]Murphy M, Hinman A, Levine AJ. Wild-type p53 negatively regulates the expression of a microtubule-associated protein. Genes Dev.1996 Dec 1; 10(23):2971-2980.
[31]Liu T, Laurell C, Selivanova G, Lundeberg J, Nilsson P, Wiman KG. Hypoxia induces p53-dependent transactivation and Fas/CD95-dependent apoptosis. Cell Death Differ.2007 Mar; 14(3):411-421.
[32]Ho JS, Ma W, Mao DY, Benchimol S. p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol Cell Biol.2005 Sep; 25(17):7423-7431.
[33]Ho J, Benchimol S. Transcriptional repression mediated by the p53 tumour suppressor. Cell Death Differ.2003 Apr; 10(4):404-408.
[34]Loyant V, Jaffre A, Breton J, Baldi I, Vital A, Chapon F, Dutoit S, Lecluse Y, Loiseau H, Lebailly P, Gauduchon P. Screening of TP53 mutations by DHPLC and sequencing in brain tumours from patients with an occupational exposure to pesticides or organic solvents. Mutagenesis.2005 Sep; 20(5):365-73.
[35]Chiou SK, Rao L, White E. Bcl-2 blocks p53-dependent apoptosis. Mol Cell Biol.1994 Apr; 14(4): 2556-2563.
[36]Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN. MicroRNA genes are transcribed by RNA polymerase Ⅱ. EMBO J.2004 Oct 13; 23(20):4051-60.
[37]Aguda BD, Kim Y, Piper-Hunter MG, Friedman A, Marsh CB. MicroRNA regulation of a cancer network:consequences of the feedback loops involving miR-17-92, E2F, and Myc. Proc Natl Acad Sci U S A.2008 Dec 16; 105(50):19678-19683.
[38]Coller HA, Forman JJ, Legesse-Miller A. "Myc'ed messages":myc induces transcription of E2F1 while inhibiting its translation via a microRNA polycistron. PLoS Genet.2007 Aug; 3(8):e146.
[39]Saikumar P, Dong Z, Patel Y, Hall K, Hopfer U, Weinberg JM, Venkatachalam MA. Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene.1998 Dec 31; 17(26):3401-15.
[40]Stempien-Otero A, Karsan A, Cornejo CJ, Xiang H, Eunson T, Morrison RS, Kay M, Winn R, Harlan J. Mechanisms of hypoxia-induced endothelial cell death. Role of p53 in apoptosis. J Biol Chem.1999 Mar 19; 274(12):8039-8045.
[41]Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A, Dannenberg AJ. Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem.1999 Apr 16; 274(16):10911-10915.
[42]Takakura S, Mitsutake N, Nakashima M, Namba H, Saenko VA, Rogounovitch TI, Nakazawa Y, Hayashi T, Ohtsuru A, Yamashita S. Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci.2008 Jun; 99(6):1147-1154.
[43]Tanzer A, Stadler PF. Molecular evolution of a microRNA cluster. J Mol Biol.2004 May 28; 339(2): 327-335.
[44]Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A.2006 Feb 14; 103(7):2257-2261.
[45]Wang L, Wu Q, Qiu P, Mirza A, McGuirk M, Kirschmeier P, Greene JR, Wang Y, Pickett CB, Liu S. Analyses of p53 target genes in the human genome by bioinformatic and microarray approaches. J Biol Chem.2001 Nov 23; 276(47):43604-43610.
[46]Weinmann M, Jendrossek V, Guner D, Goecke B, Belka C. Cyclic exposure to hypoxia and reoxygenation selects for tumor cells with defects in mitochondrial apoptotic pathways. FASEB J.2004 Dec; 18(15):1906-1908.
[47]Woods K, Thomson JM, Hammond SM. Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. J Biol Chem.2007 Jan 26; 282(4):2130-2134.
[48]Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol.2008 Apr;9(4):405-414.
[49]Yu J, Wang Z, Kinzler KW, Vogelstein B, Zhang L. PUMA mediates the apoptotic response to p53 in colorectal cancer cells. Proc Natl Acad Sci U S A.2003 Feb 18; 100(4):1931-1936.
[1]Kahi CJ, Rex DK, Imperiale TF. Screening, surveillance, and primary prevention for colorectal cancer: a review of the recent literature. Gastroenterology.2008 Aug; 135(2):380-399.
[2]Wolpin BM, Meyerhardt JA, Mamon HJ, Mayer RJ. Adjuvant treatment of colorectal cancer. CA Cancer J Clin.2007 May-Jun; 57(3):168-185.
[3]Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009 Nov-Dec; 59(6):366-78.
[4]Carpizo DR, D'Angelica M. Liver resection for metastatic colorectal cancer in the presence of extrahepatic disease. Lancet Oncol.2009 Aug; 10(8):801-809.
[5]Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol.2009 Nov 1; 27(31):5287-5297.
[6]Bessette DC, Qiu D, Pallen CJ. PRL PTPs:mediators and markers of cancer progression. Cancer Metastasis Rev.2008 Jun; 27(2):231-252.
[7]Hill RP, Marie-Egyptienne DT, Hedley DW. Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol.2009 Apr; 19(2):106-111.
[8]Nannini M, Pantaleo MA, Maleddu A, Astolfi A, Formica S, Biasco G. Gene expression profiling in colorectal cancer using microarray technologies:results and perspectives. Cancer Treat Rev.2009 May; 35(3):201-209. Epub 2008 Dec 9.
[9]Bristow RG, Hill RP. Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer.2008 Mar; 8(3):180-192.
[10]Horan AD, Koch CJ. The K(m) for Radiosensitization of Human Tumor Cells by Oxygen is Much Greater than 3 mmHg and is Further Increased by Elevated Levels of Cysteine. Radiat Res.2001 Oct; 156(4):388-398.
[11]Stockmann C, Doedens A, Weidemann A, Zhang N, Takeda N, Greenberg JI, Cheresh DA, Johnson RS. Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature.2008 Dec 11; 456(7223):814-818.
[12]Bertout JA, Patel SA, Simon MC. The impact of 02 availability on human cancer. Nat Rev Cancer. 2008 Dec; 8(12):967-975.
[13]Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer.2008 Jun; 8(6):425-437.
[14]Chaudary N, Hill RP. Hypoxia and metastasis. Clin Cancer Res.2007 Apr 1; 13(7):1947-1949.
[15]Ruan K, Song G, Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem.2009 Aug 15; 107(6):1053-1062.
[16]Chan DA, Giaccia AJ. Hypoxia, gene expression, and metastasis. Cancer Metastasis Rev.2007 Jun; 26(2):333-339.
[17]Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet.2009 Oct; 10(10):704-714.
[18]Mott JL. MicroRNAs involved in tumor suppressor and oncogene pathways:implications for hepatobiliary neoplasia. Hepatology.2009 Aug; 50(2):630-637.
[19]Segura MF, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S, Zakrzewski J, Blochin E, Rose A, Bogunovic D, Polsky D, Wei J, Lee P, Belitskaya-Levy I, Bhardwaj N, Osman I, Hernando E. Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci U S A.2009 Feb 10; 106(6): 1814-1819.
[20]Kulshreshtha R, Davuluri RV, Calin GA, Ivan M. A microRNA component of the hypoxic response. Cell Death Differ.2008 Apr; 15(4):667-671.
[21]Ivan M, Harris AL, Martelli F, Kulshreshtha R. Hypoxia response and microRNAs:no longer two separate worlds. J Cell Mol Med.2008 Sep-Oct; 12(5A):1426-1431.
[22]Mallick B, Ghosh Z, Chakrabarti J. MicroRNome analysis unravels the molecular basis of SARS infection in bronchoalveolar stem cells. PLoS One.2009 Nov 13; 4(11):e7837.
[23]Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity:microRNA biogenesis pathways and their regulation. Nat Cell Biol.2009 Mar; 11(3):228-234.
[24]Dore LC, Amigo JD, Dos Santos CO, Zhang Z, Gai X, Tobias JW, Yu D, Klein AM, Dorman C, Wu W, Hardison RC, Paw BH, Weiss MJ. A GATA-1-regulated microRNA locus essential for erythropoiesis. Proc Natl Acad Sci U S A.2008 Mar 4; 105(9):3333-3338.
[25]Sambrook J,Russell DW. Molecular Cloning:A Laboratory Manual (Third Edition).Cold Spring Harbor Laboratory Press,2001.
[26]Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature.2007 Oct 11; 449(7163):682-688.
[27]Zhu X, Asa SL, Ezzat S. Fibroblast growth factor 2 and estrogen control the balance of histone 3 modifications targeting MAGE-A3 in pituitary neoplasia. Clin Cancer Res.2008 Apr 1; 14(7): 1984-1996.
[28]Behrens C, Lin HY, Lee JJ, Raso MG, Hong WK, Wistuba Ⅱ, Lotan R. Immunohistochemical expression of basic fibroblast growth factor and fibroblast growth factor receptors 1 and 2 in the pathogenesis of lung cancer. Clin Cancer Res.2008 Oct 1; 14(19):6014-6022.
[29]Fromowitz FB, Viola MV, Chao S, Oravez S, Mishriki Y, Finkel G, Grimson R, Lundy J. ras p21 expression in the progression of breast cancer. Hum Pathol.1987 Dec; 18(12):1268-1275.
[30]Banning A, Kipp A, Schmitmeier S, Lowinger M, Florian S, Krehl S, Thalmann S, Thierbach R, Steinberg P, Brigelius-Flohe R. Glutathione Peroxidase 2 Inhibits Cyclooxygenase-2-Mediated Migration and Invasion of HT-29 Adenocarcinoma Cells but Supports Their Growth as Tumors in Nude Mice. Cancer Res.2008 Dec 1; 68(23):9746-9753.
[31]Lendahl U, Lee KL, Yang H, Poellinger L. Generating specificity and diversity in the transcriptional response to hypoxia. Nat Rev Genet.2009 Dec; 10(12):821-832.
[32]Yan HL, Xue G, Mei Q, Wang YZ, Ding FX, Liu MF, Lu MH, Tang Y, Yu HY, Sun SH. Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J.2009 Sep 16; 28(18):2719-2732.
[33]Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ. Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell. 2009 Sep 24; 35(6):856-867.
[34]Hebert C, Norris K, Scheper MA, Nikitakis N, Sauk JJ. High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol Cancer.2007 Jan 14; 6:5.
[35]Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med.2008 Nov; 14(11):1271-1277.
[36]Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC. miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol.2005 Jul; 204(1):280-285.
[37]Hanlon K, Rudin CE, Harries LW. Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL). PLoS One.2009 Sep 25; 4(9):e7169.
[38]Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A.2005 Sep 27; 102(39):13944-13949.
[39]Cao Y, Cao R, Hedlund EM. R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways. J Mol Med.2008 Jul; 86(7):785-789. Epub 2008 Apr 8.
[40]Katoh M, Katoh M. FGF signaling network in the gastrointestinal tract (review). Int J Oncol.2006 Jul; 29(1):163-168.
[41]Katoh M. Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. Stem Cell Rev.2007 Jan; 3(1):30-38.
[42]Katoh Y, Katoh M. FGF signaling inhibitor, SPRY4, is evolutionarily conserved target of WNT signaling pathway in progenitor cells. Int J Mol Med.2006 Mar; 17(3):529-532.
[1]Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell.1993 Dec 3; 75(5):843-854.
[2]Carrington JC, Ambros V. Role of microRNAs in plant and animal development. Science.2003 Jul 18; 301(5631):336-338.
[3]Griffiths-Jones S. The microRNA Registry. Nucleic Acids Res.2004 Jan 1; 32(Database issue): D109-111.
[4]Kim HH, Kuwano Y, Srikantan S, Lee EK, Martindale JL, Gorospe M. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev.2009 Aug 1; 23(15):1743-1748.
[5]Zhang C. Novel functions for small RNA molecules. Curr Opin Mol Ther.2009 Dec; 11(6):641-651.
[6]Tang JT, Fang JY. MicroRNA regulatory network in human colorectal cancer. Mini Rev Med Chem. 2009 Jul; 9(8):921-926.
[7]Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A.2004 Mar 2; 101(9):2999-3004.
[8]Li SC, Tang P, Lin WC. Intronic microRNA:discovery and biological implications. DNA Cell Biol. 2007 Apr; 26(4):195-207.
[9]Miyoshi K, Okada TN, Siomi H, Siomi MC. Characterization of the miRNA-RISC loading complex and miRNA-RISC formed in the Drosophila miRNA pathway. RNA.2009 Jul; 15(7):1282-1291.
[10]Kawamata T, Seitz H, Tomari Y. Structural determinants of miRNAs for RISC loading and slicer-independent unwinding. Nat Struct Mol Biol.2009 Sep; 16(9):953-960.
[11]Berezikov E, Liu N, Flynt AS, Hodges E, Rooks M, Hannon GJ, Lai EC. Evolutionary flux of canonical microRNAs and mirtrons in Drosophila. Nat Genet.2010 Jan; 42(1):6-9.
[12]Berezikov E, Chung WJ, Willis J, Cuppen E, Lai EC. Mammalian mirtron genes. Mol Cell.2007 Oct 26; 28(2):328-336.
[13]Sevignani C, Calin GA, Siracusa LD, Croce CM. Mammalian microRNAs:a small world for fine-tuning gene expression. Mamm Genome.2006 Mar; 17(3):189-202.
[14]Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell.2005 Nov 18; 123(4):631-640.
[15]Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol.2002 Apr 30; 12(9):735-739.
[16]Houbaviy HB, Murray MF, Sharp PA. Embryonic stem cell-specific MicroRNAs. Dev Cell.2003 Aug; 5(2):351-358.
[17]Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science.2004 Jan 2; 303(5654):83-86.
[18]Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science.2001 Oct 26; 294(5543):853-858.
[19]Kai ZS, Pasquinelli AE. MicroRNA assassins:factors that regulate the disappearance of miRNAs. Nat Struct Mol Biol.2010 Jan; 17(1):5-10.
[20]Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A.2006 Mar 14; 103(11):4034-4039.
[21]Zhang H, Li Y, Lai M. The microRNA network and tumor metastasis. Oncogene.2010 Feb 18; 29(7): 937-948.
[22]Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell.2004 Jan 23; 116(2): 281-297.
[23]Kolb FA, Zhang H, Jaronczyk K, Tahbaz N, Hobman TC, Filipowicz W. Human dicer:purification, properties, and interaction with PAZ PIWI domain proteins. Methods Enzymol.2005; 392:316-336.
[24]Zhang B, Pan X. Expression of microRNAs in cotton. Mol Biotechnol.2009 Jul; 42(3):269-274.
[25]Kutter C, Svoboda P. miRNA, siRNA, piRNA:Knowns of the unknown. RNA Biol.2008 Oct-Dec; 5(4):181-188.
[26]Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol.1999 Dec 15; 216(2):671-680.
[27]Steitz JA, Vasudevan S. miRNPs:versatile regulators of gene expression in vertebrate cells. Biochem Soc Trans.2009 Oct; 37(Pt 5):931-935.
[28]Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J, Di Padova F, Lin SC, Gram H; Han J. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell.2005 Mar 11; 120(5):623-634.
[29]Carthew RW, Sontheimer EJ. Origins and Mechanisms of miRNAs and siRNAs. Cell.2009 Feb 20; 136(4):642-655.
[30]Huang J, Hao P, Chen H, Hu W, Yan Q, Liu F, Han ZG. Genome-wide identification of Schistosoma japonicum microRNAs using a deep-sequencing approach. PLoS One.2009 Dec 8; 4(12):e8206.
[31]Joshi T, Yan Z, Libault M, Jeong DH, Park S, Green PJ, Sherrier DJ, Farmer A, May G, Meyers BC, Xu D, Stacey G. Prediction of novel miRNAs and associated target genes in Glycine max. BMC Bioinformatics.2010 Jan 18; 11 Suppl 1:S14.
[32]Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science.2001 Oct 26; 294(5543):862-864.
[33]Michael MZ. Cloning microRNAs from mammalian tissues. Methods Mol Biol.2006; 342:189-207.
[34]Hafner M, Landgraf P, Ludwig J, Rice A, Ojo T, Lin C, Holoch D, Lim C, Tuschl T. Identification of microRNAs and other small regulatory RNAs using cDNA library sequencing. Methods.2008 Jan; 44(1):3-12.
[35]Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, Cha KY, Chung HM, Yoon HS, Moon SY, Kim VN, Kim KS. Human embryonic stem cells express a unique set of microRNAs. Dev Biol.2004 Jun 15; 270(2):488-498.
[36]Yoon S, De Micheli G. Computational identification of microRNAs and their targets. Birth Defects Res C Embryo Today.2006 Jun; 78(2):118-128.
[37]Lim LP, Lau NC, Weinstein EG, Abdelhakim A, Yekta S, Rhoades MW, Burge CB, Bartel DP. The microRNAs of Caenorhabditis elegans. Genes Dev.2003 Apr 15; 17(8):991-1008.
[38]Grad Y, Aach J, Hayes GD, Reinhart BJ, Church GM, Ruvkun G, Kim J. Computational and experimental identification of C. elegans microRNAs. Mol Cell.2003 May; 11(5):1253-63.
[39]Zhang BH, Pan XP, Cox SB, Cobb GP, Anderson TA. Evidence that miRNAs are different from other RNAs. Cell Mol Life Sci.2006 Jan; 63(2):246-254.
[40]Bentwich I. Prediction and validation of microRNAs and their targets. FEBS Lett.2005 Oct 31; 579(26):5904-5910.
[41]Watanabe Y, Tomita M, Kanai A. Computational methods for microRNA target prediction. Methods Enzymol.2007; 427:65-86.
[42]Stark A, Brennecke J, Russell RB, Cohen SM. Identification of Drosophila MicroRNA targets. PLoS Biol.2003 Dec; 1(3):E60.
[43]John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA targets. PLoS Biol. 2004 Nov; 2(11):e363.
[44]Xia W, Cao G, Shao N. Progress in miRNA target prediction and identification. Sci China C Life Sci. 2009 Dec; 52(12):1123-1130.
[45]Wark AW, Lee HJ, Corn RM. Multiplexed detection methods for profiling microRNA expression in biological samples. Angew Chem Int Ed Engl.2008; 47(4):644-652.
[46][15] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods.2001 Dec; 25(4):402-408.
[47]Bandres E, Cubedo E, Agirre X, Malumbres R, Zarate R, Ramirez N, Abajo A, Navarro A, Moreno 1, Monzo M, Garcia-Foncillas J. Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer.2006 Jul 19; 5:29.
[48]Lao K, Xu NL, Yeung V, Chen C, Livak KJ, Straus NA. Multiplexing RT-PCR for the detection of multiple miRNA species in small samples. Biochem Biophys Res Commun.2006 Apr 28; 343(1): 85-89.
[49]Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A.2004 Jun 29; 101(26):9740-9744.
[50]Li W, Ruan K. MicroRNA detection by microarray. Anal Bioanal Chem.2009 Jun; 394(4): 1117-1124.
[51]Yamayoshi A, Momokawa D, Kobori A, Murakami A. Development of peptide-oligonucleotide conjugates for regulation of small RNA function. Nucleic Acids Symp Ser (Oxf).2009; (53):53-54.
[52]Orom UA, Lund AH. Isolation of microRNA targets using biotinylated synthetic microRNAs. Methods.2007 Oct; 43(2):162-165.
[53]Marquez RT, McCaffrey AP. Advances in microRNAs:implications for gene therapists. Hum Gene Ther.2008 Jan; 19(1):27-38.
[54]Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, Bozzoni I. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell.2005 Dec 2; 123(5):819-831.
[55]Wang B, Doench JG, Novina CD. Analysis of microRNA effector functions in vitro. Methods.2007 Oct; 43(2):91-104.
[56]Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science.2004 Apr 23; 304(5670):594-596.
[57]Cowland JB, Hother C, Grenbaek K. MicroRNAs and cancer. APMIS.2007 Oct; 115(10): 1090-1106.
[58]Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet.2007 May; 39(5):673-677.
[59]Voorhoeve PM. MicroRNAs:Oncogenes, tumor suppressors or master regulators of cancer heterogeneity? Biochim Biophys Acta.2010 Jan; 1805(1):72-86.
[60]Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell.2008 Apr 18; 133(2):217-222.
[61]Ernst A, Campos B, Meier J, Devens F, Liesenberg F, Wolter M, Reifenberger G, Herold-Mende C, Lichter P, Radlwimmer B. De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures. Oncogene.2010 Mar 22. [Epub ahead of print]
[62]Aguda BD, Kim Y, Piper-Hunter MG, Friedman A, Marsh CB. MicroRNA regulation of a cancer network:consequences of the feedback loops involving miR-17-92, E2F, and Myc. Proc Natl Acad Sci U S A.2008 Dec 16; 105(50):19678-19683.
[63]Yan HL, Xue G, Mei Q, Wang YZ, Ding FX, Liu MF, Lu MH, Tang Y, Yu HY, Sun SH. Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J. 2009 Sep 16; 28(18):2719-2732.
[64]Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun.2005 Sep 9; 334(4):1351-1358.
[65]Qi L, Bart J, Tan LP, Platteel I, Sluis T, Huitema S, Harms Q Fu L, Hollema H, Berg A. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma. BMC Cancer.2009 May 28; 9:163.
[66]Krichevsky AM, Gabriely G. miR-21:a small multi-faceted RNA. J Cell Mol Med.2009 Jan;13(1):39-53.
[67]Loffler D, Brocke-Heidrich K, Pfeifer G, Stocsits C, Hackermuller J, Kretzschmar AK, Burger R, Gramatzki M, Blumert C, Bauer K, Cvijic H, Ullmann AK, Stadler PF, Horn F. Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood.2007 Aug 15; 110(4):1330-1333.
[68]Tili E, Croce CM, Michaille JJ. miR-155:on the crosstalk between inflammation and cancer. Int Rev Immunol.2009; 28(5):264-284.
|69] Kluiver J, Haralambieva E, de Jong D, Blokzijl T, Jacobs S, Kroesen BJ, Poppema S, van den Berg A. Lack of BIC and microRNA miR-155 expression in primary cases of Burkitt lymphoma. Genes Chromosomes Cancer.2006 Feb; 45(2):147-153.
[70]Roush S, Slack FJ. The let-7 family of microRNAs. Trends Cell Biol.2008 Oct; 18(10):505-516.
[71]Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ. RAS is regulated by the let-7 microRNA family. Cell.2005 Mar 11; 120(5): 635-647.
[72]Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res.2004 Jun 1; 64(11): 3753-3756.
[73]Boyerinas B, Park SM, Shomron N, Hedegaard MM, Vinther J, Andersen JS, Feig C, Xu J, Burge CB, Peter ME. Identification of let-7-regulated oncofetal genes. Cancer Res.2008 Apr 15; 68(8): 2587-2591.
[74]Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer:discovery, function and future perspectives. Cell Death Differ.2010 Feb; 17(2):215-220.
[75]Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A.2008 Apr 1; 105(13):5166-5171.
[76]Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC. miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol.2005 Jul; 204(1):280-285.
[77]Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A.2005 Sep 27; 102(39): 13944-13949.
[78]Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med.2008 Nov; 14(11):1271-1277.
[79]Bartels CL, Tsongalis GJ. MicroRNAs:novel biomarkers for human cancer. Clin Chem.2009 Apr; 55(4):623-631.
[80]Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, Morgan DL, Postier RG, Brackett DJ, Schmittgen TD. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer.2007 Mar 1; 120(5):1046-1054.
[81]Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature.2005 Jun 9; 435(7043):834-838.
[82]Bottoni A, Zatelli MC, Ferracin M, Tagliati F, Piccin D, Vignali C, Calin GA, Negrini M, Croce CM, Degli Uberti EC. Identification of differentially expressed microRNAs by microarray:a possible role for microRNA genes in pituitary adenomas. J Cell Physiol.2007 Feb; 210(2):370-377.
[83]Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell'Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A.2004 Aug 10; 101(32):11755-11760.
[84]Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, Calin GA, Volinia S, Liu CG, Scarpa A, Croce CM. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol.2006 Oct 10; 24(29):4677-4684.
[85]Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA.2007 May 2; 297(17):1901-1908.
[86]Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell.2006 Mar; 9(3):189-198.
[87]Trang P, Weidhaas JB, Slack FJ. MicroRNAs as potential cancer therapeutics. Oncogene.2008 Dec; 27 Suppl 2:S52-57.
[88]Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC. Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem. 2007 Jan 12; 282(2):1479-1486.
[89]Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with'antagomirs'. Nature.2005 Dec 1; 438(7068):685-9.
[90]Hummel R, Hussey DJ, Haier J. MicroRNAs:predictors and modifiers of chemo-and radiotherapy in different tumour types. Eur J Cancer.2010 Jan; 46(2):298-311.
[91]Li C, Feng Y, Coukos G, Zhang L. Therapeutic microRNA strategies in human cancer. AAPS J.2009 Dec; 11(4):747-757.
[92]Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P, Salazar F, Kay MA. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature. 2006 May 25; 441(7092):537-541.
[93]Stenvang J, Silahtaroglu AN, Lindow M, Elmen J, Kauppinen S. The utility of LNA in microRNA-based cancer diagnostics and therapeutics. Semin Cancer Biol.2008 Apr; 18(2):89-102.
[94]Grimm D, Kay MA. RNAi and gene therapy:a mutual attraction. Hematology Am Soc Hematol Educ Program.2007:473-481.
[95]Aagaard L, Rossi JJ. RNAi therapeutics:principles, prospects and challenges. Adv Drug Deliv Rev. 2007 Mar 30; 59(2-3):75-86.
[96]Wu X, Xiao H. miRNAs modulate the drug response of tumor cells. Sci China C Life Sci.2009 Sep; 52(9):797-801.
[97]Fojo T. Multiple paths to a drug resistance phenotype:mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs. Drug Resist Updat.2007 Feb-Apr; 10(1-2):59-67.
[98]Svoboda M, Izakovicova Holla L, Sefr R, Vrtkova I, Kocakova I, Tichy B, Dvorak J. Micro-RNAs miR125b and miR137 are frequently upregulated in response to capecitabine chemoradiotherapy of rectal cancer. Int J Oncol.2008 Sep; 33(3):541-547.
[99]Nasser MW, Datta J, Nuovo G, Kutay H, Motiwala T, Majumder S, Wang B, Suster S, Jacob ST, Ghoshal K. Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem.2008 Nov 28; 283(48):33394-33405.
[100]Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene.2007 Apr 26; 26(19):2799-2803.
[101]Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, Jiang J, Schmittgen TD, Patel T. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology.2006 Jun; 130(7):2113-2129.
[102]Rokhlin OW, Scheinker VS, Taghiyev AF, Bumcrot D, Glover RA, Cohen MB. MicroRNA-34 mediates AR-dependent p53-induced apoptosis in prostate cancer. Cancer Biol Ther.2008 Aug; 7(8): 1288-1296.
[103]Iorio MV, Croce CM. MicroRNAs in cancer:small molecules with a huge impact. J Clin Oncol.2009 Dec 1; 27(34):5848-5856.
[104]Weiss GJ, Bemis LT, Nakajima E, Sugita M, Birks DK, Robinson WA, Varella-Garcia M, Bunn PA Jr, Haney J, Helfrich BA, Kato H, Hirsch FR, Franklin WA. EGFR regulation by microRNA in lung cancer:correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. Ann Oncol.2008 Jun; 19(6):1053-1059.
[105]Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem. 2008 Oct 31; 283(44):29897-28903.
[106]Zhao JJ, Lin J, Yang H, Kong W, He L, Ma X, Coppola D, Cheng JQ. MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem.2008 Nov 7; 283(45):31079-31086.
[107]Thorburn A, Behbakht K, Ford H. TRAIL receptor-targeted therapeutics:resistance mechanisms and strategies to avoid them. Drug Resist Updat.2008 Feb-Apr; 11(1-2):17-24.
[108]Garofalo M, Quintavalle C, Di Leva G, Zanca C, Romano G, Taccioli C, Liu CG, Croce CM, Condorelli G. MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene.2008 Jun 19; 27(27):3845-3855.
[109]Corsten MF, Miranda R, Kasmieh R, Krichevsky AM, Weissleder R, Shah K. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res.2007 Oct 1; 67(19):8994-9000.