MicroRNA145对骨肉瘤细胞增殖和转移等生物学行为的影响及相关机制研究
|
摘要
第一部分MicroRNA-145和血管内皮生长因子(VEGF)在人骨肉瘤组织中的表达变化
目的：探讨人骨肉瘤组织microRNA-145(miRNA-145)和VEGF表达的变化及其临床意义。
方法：临床上收集华中科技大学附属协和医院28例人骨肉瘤标本,用实时荧光定量RT-PCR的方法检测28例骨肉瘤标本中骨肉瘤组织,肿瘤边缘组织,正常组织中miRNA-145的表达变化；用实时荧光定量RT-PCR以及免疫组织化学的方法检测28例骨肉瘤标本中骨肉瘤组织,肿瘤边缘组织,正常组织中VEGF的表达变化。
结果：28例标本中25例骨肉瘤组织中miRNA-145的表达较正常组织明显降低,肿瘤边缘组织中的表达位于两者之间,有统计学意义(P<0.05)。28例标本中所有骨肉瘤组织中VEGF的表达较正常组织中明显增高,肿瘤边缘组织中的表达位于两者之间,有统计学意义(P<0.05)。
结论：骨肉瘤组织中的miRNA-145的表达下调,VEGF的表达上调,miRNA-145和VEGF参与骨肉瘤的发生发展,两者之间可能存在着联系。
第二部分MicroRNA-145对骨肉瘤细胞生物学行为影响的体外实验研究
目的：研究microRNA-145(miRNA-145)对于骨肉瘤细胞生物学行为包括细胞增殖、细胞周期、凋亡、粘附侵袭以及促血管形成能力的影响。
方法：用脂质体法将miRNA-145模拟物瞬时转染入人骨肉瘤细胞(MG63)中,实验设置空白对照组、阴性对照转染组、miRNA-145转染组三组,转染后荧光显微镜下观察转染效率,实时荧光定量RT-PCR检测各组细胞miRNA-145的表达,蛋白质印迹法Western Blot检测各组细胞VEGF的表达,MTT增殖实验检测各组细胞的增殖情况,流式细胞仪检测各组细胞周期及细胞凋亡率,细胞粘附实验检测各组细胞的粘附能力,Transwell细胞侵袭实验检测各组细胞的侵袭能力,小管形成实验检测各组细胞的促进血管生成能力。
结果：MiRNA-145转染组中miRNA-145的表达明显增高,VEGF的表达明显降低,有统计学意义(P<0.05)；MiRNA-145转染组中肿瘤细胞增殖速度明显下降,细胞周期停止在G1期之前,凋亡率增高,细胞粘附力和侵袭力明显降低,促进血管生成能力明显降低,有统计学意义(P<0.05)。
结论：MiRNA-145可以有效的抑制骨肉瘤细胞的增殖、粘附、侵袭和促血管形成能力,促进细胞凋亡,miRNA-145是一种骨肉瘤抑制基因,miRNA-145和VEGF之间可能存在相关调控关系。
第三部分MicroRNA-145调控骨肉瘤中血管内皮生长因子(VEGF)表达的实验研究
目的：探讨骨肉瘤中microRNA-145(miRNA-145)对于VEGF表达的相关调控关系。
方法：采用荧光素酶报告基因检测方法,构建含有VEGF-3'UTR的表达质粒(包括野生型和突变体),将含有VEGF-3'UTR的质粒与miRNA-145共转染入人骨肉瘤细胞中,实验分为三组：单纯质粒转染组,含有VEGF-3'UTR质粒和miRNA-145阴性对照共转染组,含有VEGF-3'UTR和miRNA-145共转染组,转染后48小时监测各组细胞荧光素酶的表达变化。
结果：含有VEGF-3'UTR的表达质粒(野生型)与miRNA-145共转染组荧光素酶的表达较其他两组明显降低,有统计学意义(P<0.05),而含有VEGF-3'UTR突变体的表达质粒与miRNA-145共转染组荧光素酶的表达与其他两组相比较无明显变化(P>0.05)。
结论：MiRNA-145可以与VEGF的3'-UTR不完全互补结合,下调骨肉瘤中VEGF的表达,VEGF是miRNA-145的一个靶基因。
第四部分MicroRNA-145对骨肉瘤细胞生物学行为影响的体内实验研究
目的：研究microRNA-145(miRNA-145)对于裸鼠体内骨肉瘤细胞生长和微血管形成的影响。
方法：Balb/c裸小鼠16只,随机分为对照组和实验组,每组8只,对照组用未转染的MG63细胞建立骨肉瘤模型,实验组用转染miRNA-145模拟物的MG63细胞建立骨肉瘤模型。荷瘤裸鼠饲养4周,比较两组成瘤率,瘤体大小,瘤体重量,用免疫组织化学的检测方法检测两组裸鼠瘤体Ⅷ因子和VEGF的表达,并计算微血管密度(MVD)。
结果：对照组裸鼠成瘤率87.5%,实验组裸鼠成瘤率37.5%,实验组裸鼠形成肿瘤大小,重量明显低于对照组,实验组形成肿瘤VEGF的表达较对照组明显降低,MVD计数明显降低,有统计学意义(P<0.05)。
结论：MiRNA-145可以抑制荷瘤裸鼠的成瘤率,抑制肿瘤的体内生长和肿瘤血管的形成。
Part1The expression of microRNA-145and vascular endothelial growth factor (VEGF) in osteosarcoma tissues
Objective:To investigate the expression of microRNA-145(miRNA-145) and vascular endothelial growth factor (VEGF) in osteosarcoma tissues.
Methods:Twenty-eight osteosarcoma tissue samples diagnosed by pathological examination and28normorl bone tissue samples from the same patients were investigated. The expression of miRNA-145were detected in osteosarcoma tissues, the edge of osteosarcoma tissues and normal tissues by quantitative real-time RT-PCR analysis.The expression of VEGF were detected in osteosarcoma tissues, the edge of osteosarcoma tissues and normal tissues by quantitative real-time RT-PCR analysis and immunohistochemistry.
Results:Under-expression of miRNA-145was observed in25of28osteosarcoma tissues in comparison with the corresponding normal tissues. MiRNA-145expression in the edge of osteosarcoma tissues was more than that in tumor tissues but less than that in the normal tissues. Over-expression of VEGF was observed in28osteosarcoma tissues in comparison with the corresponding normal tissues. VEGF expression in the edge of osteosarcoma tissues was less than that in tumor tissues but more than that in the normal tissues. The differences were all statistically significant(P<0.05).
Conclusions:MiRNA-145is under-expressed in osteosarcoma tissues and VEGF is over-expressed in osteosarcoma tissues. MiRNA-145and VEGF are participated in the occurrence and development of osteosarcoma. MiRNA-145and VEGF may have correlated control relationships.
Part2The effects of microRNA-145on the biological behaviour of osteosarcoma cells in vitro
Objective:To investigate the effects of microRNA-145(miRNA-145) on the proliferation, apoptosis, adhesiveness, invasiveness and angiogenesis of osteosarcoma cells (MG63) in vitro.
Methods:MG63cells were randomly allocated into3groups:blank group(non-transfected group), negative control transfected group and miRNA-145transfected group. The cells in miRNA-145transfected and negative control transfected groups were transfected with the miRNA-145mimics and mimics negative control respectively, by using Lipofectamine2000according to the manufacturer's instruction. After transfection, transfection efficiency was observed.MiRNA-145expression level was detected by quantitative real-time RT-PCR. VEGF expression level was detected by Western Blot. Cell proliferation was detected by MTT proliferation assay. Cell cycle and apoptosis of MG63cells in each group were detected by flow cytometry. The adhesiveness and invasiveness of cells were detected by cell adhesion assay and transwell invasion assay respectively. Angiogenesis were detected by endothelial cell tube formation assay.
Results:MiRNA-145expression in the miRNA-145transfected group was significantly up-regulated compared to the blank group and negative control group(P<0.05). VEGF expression in the miRNA-145transfected group was significantly down-regulated compared to blank group and negative control group(P<0.05). Meanwhile, cell proliferation, cycle and apoptosis, adhesiveness, invasiveness and angiogenesis of osteosarcoma cells were all significantly inhibited in the miRNA-145transfected group(P<0.05).
Conclusions:MiRNA-145can dramatically inhibit proliferation, apoptosis adhesiveness, invasiveness and angiogenesis of osteosarcoma cells. MiRNA-145can promote apoptosis of osteosarcoma cells.MiRNA-145is a tumor suppressor gene for osteosarcoma.
Part3The study of regulatory relationship of miRNA-145on VEGF expression in osteosarcoma
Objective:To investigate the effect of miRNA-145on VEGF expression in osteosarcoma.
Methods:The luciferase-UTR reporter constructs were generated by introducing the VEGF-3'UTR containing the wild-type and mutant into pMiR-Report vector. MG63cells were cotransfected with the pMiR-report vector containing the3'-UTR variants and microRNA-145mimics or mimics negative control. Experiments were divided into three groups:blank group(plasmid transfected group), negative control and plasmid cotransfected group, plasmid and miRNA-145cotransfected group.Luciferase activity was measured48h after transfection using the Dual-Glo luciferase assay system according to manufacturer's instructions.
Results:After co-transfection with pMiR-report vectors and miRNA-145or negative control, the cells over-expressing miRNA-145were observed with a significant decline in luciferase activity compared to other control groups(P<0.05).
Conclusions:MiRNA-145regulate VEGF expression at the translational level by interacting with the3'UTR of VEGF in osteosarcoma. VEGF is a direct target gene of microRNA-145.
Part4The effects of microRNA-145on the biological behaviour of osteosarcoma cells in vivo
Objective:To investigate the effects of microRNA-145(miRNA-145) on the growth and angiogenesis of osteosarcoma in vivo.
Methods:Sixteen nude mice(Balb/c) were randomly divided into2groups, experimental group and control group,8mice in each group. The animal model of experimental group was constructed by subcutaneous inoculation of osteosarcoma cells transfected with miRNA-145into nude mice and control group by subcutaneous inoculation of osteosarcoma cells.The osteosarcoma-bearing nude mice were feeded for4weeks. After4weeks, tumor formation rate, size and weight of tumor were observed in each group. VIII factor expression and VEGF expression of tumor were detected by immunohistochemistry and microvessel density were calculated.
Results:The tumor formation rate in control group is87.5%and experimental group is37.5%.The size and weight of tumor in experimental group is significantly less than control group(P<0.05). The VEGF expression and MVD of tumor in experimental group is significantly lower than those in control group(P<0.05).
Conclusions:MiRNA-145can inhibit the osteosarcoma formation rate of nude mice, and inhibit the growth and angiopoiesis of tumor in vivo.
目的：探讨人骨肉瘤组织microRNA-145(miRNA-145)和VEGF表达的变化及其临床意义。
方法：临床上收集华中科技大学附属协和医院28例人骨肉瘤标本,用实时荧光定量RT-PCR的方法检测28例骨肉瘤标本中骨肉瘤组织,肿瘤边缘组织,正常组织中miRNA-145的表达变化；用实时荧光定量RT-PCR以及免疫组织化学的方法检测28例骨肉瘤标本中骨肉瘤组织,肿瘤边缘组织,正常组织中VEGF的表达变化。
结果：28例标本中25例骨肉瘤组织中miRNA-145的表达较正常组织明显降低,肿瘤边缘组织中的表达位于两者之间,有统计学意义(P<0.05)。28例标本中所有骨肉瘤组织中VEGF的表达较正常组织中明显增高,肿瘤边缘组织中的表达位于两者之间,有统计学意义(P<0.05)。
结论：骨肉瘤组织中的miRNA-145的表达下调,VEGF的表达上调,miRNA-145和VEGF参与骨肉瘤的发生发展,两者之间可能存在着联系。
第二部分MicroRNA-145对骨肉瘤细胞生物学行为影响的体外实验研究
目的：研究microRNA-145(miRNA-145)对于骨肉瘤细胞生物学行为包括细胞增殖、细胞周期、凋亡、粘附侵袭以及促血管形成能力的影响。
方法：用脂质体法将miRNA-145模拟物瞬时转染入人骨肉瘤细胞(MG63)中,实验设置空白对照组、阴性对照转染组、miRNA-145转染组三组,转染后荧光显微镜下观察转染效率,实时荧光定量RT-PCR检测各组细胞miRNA-145的表达,蛋白质印迹法Western Blot检测各组细胞VEGF的表达,MTT增殖实验检测各组细胞的增殖情况,流式细胞仪检测各组细胞周期及细胞凋亡率,细胞粘附实验检测各组细胞的粘附能力,Transwell细胞侵袭实验检测各组细胞的侵袭能力,小管形成实验检测各组细胞的促进血管生成能力。
结果：MiRNA-145转染组中miRNA-145的表达明显增高,VEGF的表达明显降低,有统计学意义(P<0.05)；MiRNA-145转染组中肿瘤细胞增殖速度明显下降,细胞周期停止在G1期之前,凋亡率增高,细胞粘附力和侵袭力明显降低,促进血管生成能力明显降低,有统计学意义(P<0.05)。
结论：MiRNA-145可以有效的抑制骨肉瘤细胞的增殖、粘附、侵袭和促血管形成能力,促进细胞凋亡,miRNA-145是一种骨肉瘤抑制基因,miRNA-145和VEGF之间可能存在相关调控关系。
第三部分MicroRNA-145调控骨肉瘤中血管内皮生长因子(VEGF)表达的实验研究
目的：探讨骨肉瘤中microRNA-145(miRNA-145)对于VEGF表达的相关调控关系。
方法：采用荧光素酶报告基因检测方法,构建含有VEGF-3'UTR的表达质粒(包括野生型和突变体),将含有VEGF-3'UTR的质粒与miRNA-145共转染入人骨肉瘤细胞中,实验分为三组：单纯质粒转染组,含有VEGF-3'UTR质粒和miRNA-145阴性对照共转染组,含有VEGF-3'UTR和miRNA-145共转染组,转染后48小时监测各组细胞荧光素酶的表达变化。
结果：含有VEGF-3'UTR的表达质粒(野生型)与miRNA-145共转染组荧光素酶的表达较其他两组明显降低,有统计学意义(P<0.05),而含有VEGF-3'UTR突变体的表达质粒与miRNA-145共转染组荧光素酶的表达与其他两组相比较无明显变化(P>0.05)。
结论：MiRNA-145可以与VEGF的3'-UTR不完全互补结合,下调骨肉瘤中VEGF的表达,VEGF是miRNA-145的一个靶基因。
第四部分MicroRNA-145对骨肉瘤细胞生物学行为影响的体内实验研究
目的：研究microRNA-145(miRNA-145)对于裸鼠体内骨肉瘤细胞生长和微血管形成的影响。
方法：Balb/c裸小鼠16只,随机分为对照组和实验组,每组8只,对照组用未转染的MG63细胞建立骨肉瘤模型,实验组用转染miRNA-145模拟物的MG63细胞建立骨肉瘤模型。荷瘤裸鼠饲养4周,比较两组成瘤率,瘤体大小,瘤体重量,用免疫组织化学的检测方法检测两组裸鼠瘤体Ⅷ因子和VEGF的表达,并计算微血管密度(MVD)。
结果：对照组裸鼠成瘤率87.5%,实验组裸鼠成瘤率37.5%,实验组裸鼠形成肿瘤大小,重量明显低于对照组,实验组形成肿瘤VEGF的表达较对照组明显降低,MVD计数明显降低,有统计学意义(P<0.05)。
结论：MiRNA-145可以抑制荷瘤裸鼠的成瘤率,抑制肿瘤的体内生长和肿瘤血管的形成。
Part1The expression of microRNA-145and vascular endothelial growth factor (VEGF) in osteosarcoma tissues
Objective:To investigate the expression of microRNA-145(miRNA-145) and vascular endothelial growth factor (VEGF) in osteosarcoma tissues.
Methods:Twenty-eight osteosarcoma tissue samples diagnosed by pathological examination and28normorl bone tissue samples from the same patients were investigated. The expression of miRNA-145were detected in osteosarcoma tissues, the edge of osteosarcoma tissues and normal tissues by quantitative real-time RT-PCR analysis.The expression of VEGF were detected in osteosarcoma tissues, the edge of osteosarcoma tissues and normal tissues by quantitative real-time RT-PCR analysis and immunohistochemistry.
Results:Under-expression of miRNA-145was observed in25of28osteosarcoma tissues in comparison with the corresponding normal tissues. MiRNA-145expression in the edge of osteosarcoma tissues was more than that in tumor tissues but less than that in the normal tissues. Over-expression of VEGF was observed in28osteosarcoma tissues in comparison with the corresponding normal tissues. VEGF expression in the edge of osteosarcoma tissues was less than that in tumor tissues but more than that in the normal tissues. The differences were all statistically significant(P<0.05).
Conclusions:MiRNA-145is under-expressed in osteosarcoma tissues and VEGF is over-expressed in osteosarcoma tissues. MiRNA-145and VEGF are participated in the occurrence and development of osteosarcoma. MiRNA-145and VEGF may have correlated control relationships.
Part2The effects of microRNA-145on the biological behaviour of osteosarcoma cells in vitro
Objective:To investigate the effects of microRNA-145(miRNA-145) on the proliferation, apoptosis, adhesiveness, invasiveness and angiogenesis of osteosarcoma cells (MG63) in vitro.
Methods:MG63cells were randomly allocated into3groups:blank group(non-transfected group), negative control transfected group and miRNA-145transfected group. The cells in miRNA-145transfected and negative control transfected groups were transfected with the miRNA-145mimics and mimics negative control respectively, by using Lipofectamine2000according to the manufacturer's instruction. After transfection, transfection efficiency was observed.MiRNA-145expression level was detected by quantitative real-time RT-PCR. VEGF expression level was detected by Western Blot. Cell proliferation was detected by MTT proliferation assay. Cell cycle and apoptosis of MG63cells in each group were detected by flow cytometry. The adhesiveness and invasiveness of cells were detected by cell adhesion assay and transwell invasion assay respectively. Angiogenesis were detected by endothelial cell tube formation assay.
Results:MiRNA-145expression in the miRNA-145transfected group was significantly up-regulated compared to the blank group and negative control group(P<0.05). VEGF expression in the miRNA-145transfected group was significantly down-regulated compared to blank group and negative control group(P<0.05). Meanwhile, cell proliferation, cycle and apoptosis, adhesiveness, invasiveness and angiogenesis of osteosarcoma cells were all significantly inhibited in the miRNA-145transfected group(P<0.05).
Conclusions:MiRNA-145can dramatically inhibit proliferation, apoptosis adhesiveness, invasiveness and angiogenesis of osteosarcoma cells. MiRNA-145can promote apoptosis of osteosarcoma cells.MiRNA-145is a tumor suppressor gene for osteosarcoma.
Part3The study of regulatory relationship of miRNA-145on VEGF expression in osteosarcoma
Objective:To investigate the effect of miRNA-145on VEGF expression in osteosarcoma.
Methods:The luciferase-UTR reporter constructs were generated by introducing the VEGF-3'UTR containing the wild-type and mutant into pMiR-Report vector. MG63cells were cotransfected with the pMiR-report vector containing the3'-UTR variants and microRNA-145mimics or mimics negative control. Experiments were divided into three groups:blank group(plasmid transfected group), negative control and plasmid cotransfected group, plasmid and miRNA-145cotransfected group.Luciferase activity was measured48h after transfection using the Dual-Glo luciferase assay system according to manufacturer's instructions.
Results:After co-transfection with pMiR-report vectors and miRNA-145or negative control, the cells over-expressing miRNA-145were observed with a significant decline in luciferase activity compared to other control groups(P<0.05).
Conclusions:MiRNA-145regulate VEGF expression at the translational level by interacting with the3'UTR of VEGF in osteosarcoma. VEGF is a direct target gene of microRNA-145.
Part4The effects of microRNA-145on the biological behaviour of osteosarcoma cells in vivo
Objective:To investigate the effects of microRNA-145(miRNA-145) on the growth and angiogenesis of osteosarcoma in vivo.
Methods:Sixteen nude mice(Balb/c) were randomly divided into2groups, experimental group and control group,8mice in each group. The animal model of experimental group was constructed by subcutaneous inoculation of osteosarcoma cells transfected with miRNA-145into nude mice and control group by subcutaneous inoculation of osteosarcoma cells.The osteosarcoma-bearing nude mice were feeded for4weeks. After4weeks, tumor formation rate, size and weight of tumor were observed in each group. VIII factor expression and VEGF expression of tumor were detected by immunohistochemistry and microvessel density were calculated.
Results:The tumor formation rate in control group is87.5%and experimental group is37.5%.The size and weight of tumor in experimental group is significantly less than control group(P<0.05). The VEGF expression and MVD of tumor in experimental group is significantly lower than those in control group(P<0.05).
Conclusions:MiRNA-145can inhibit the osteosarcoma formation rate of nude mice, and inhibit the growth and angiopoiesis of tumor in vivo.
引文
I. Ottaviani G, Jaffe N.The epidemiology of osteosarcoma. Cancer Treat Res. 2009,152:3-13. Review.
2.范磊,邵增务.小分子干扰RNA基因沉默与骨肉瘤治疗.国际骨科学杂志.2011,32(1)：30-32.
3.范磊,吴强,魏玉龙,等.MicroRNA-145对骨肉瘤细胞增殖及凋亡的影响.中国癌症杂志.2012,22(4)：247-249.
4. Jeanteur P. miRNAs and cancer. Bull Cancer.2010,97(11):1231-1239.
5. Volk N, Shomron N. Versatility of MicroRNA Biogenesis. PLoS One 2011;6(5):e19391.
6. Wang X, Tang S, Le SY,et al.Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 2008,3(7):e2557.
7. Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep.2006,16(4):845-850.
8. Takagi T, Iio A, Nakagawa Y, et al.Decreased expression of microRNA-143 and-145 in human gastric cancers. Oncology.2009,77(1):12-21.
9. Anne Saaristo, Terhi Karpanen, Kari Alitalo. Mechanisms of angiogenesis and their use in the inhibition of tumor growth and metastasis.Oncogene.2000,19(53):6122-6129.
10. Mei J, Gao Y, Zhang L, Cai X,et al. VEGF-siRNA silencing induces apoptosis, inhibits proliferation and suppresses vasculogenic mimicry in osteosarcoma in vitro.Exp Oncol. 2008,30(1):29-34.
11. 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;25(4):402-408.
12. Calin GA, Sevignani C, Dumitru CD,et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA.2004,101(9):2999-3004.
13. Volpicelli P, Latagliata R, Carmosino I, et al. Familial occurrence of myelodysplastic syndrome with del(5q).Leuk Lymphoma.2011,52(6):1143-1145.
14. Sachdeva M, Mo YY. MiR-145-mediated suppression of cell growth, invasion and metastasis. Am J Transl Res.2010,2(2):170-180.
15. Sachdeva M, Mo YY. MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res.2010,70(1):378-387.
16. Shi B, Sepp-Lorenzino L, Prisco M,et al. MicroRNA-145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem.2007, 282(45):32582-32590.
17. Dallago CM, Oliveira MC, et al. Angiogenesis in craniopharyngiomas:Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin. Endocr Pathol.2005,16(4):355-362.
18. Avetisov SE, Mamikoian VR, Surguch BK,et al. Antiangiogenic therapy for choroidal neovascularization induced by age-related macular degeneration (preliminary communication). Vestn Oftalmol.2009,125(6):3-8.
19. Lin EY, Li JF, Bricard Qet al. Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages.Mol Oncol.2007,1(3):288-302.
1. Ottaviani G, Jaffe N.The epidemiology of osteosarcoma. Cancer Treat Res. 2009,152:3-13. Review.
2.范磊,邵增务.小分子干扰RNA基因沉默与骨肉瘤治疗.国际骨科学杂志.2011,32(1)：30-32.
3.范磊,吴强,魏玉龙,等.MicroRNA-145对骨肉瘤细胞增殖及凋亡的影响.中国癌症杂志.2012,22(4)：247-249.
4. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell 2004,116(2):281-297.
5. Zeng Y. Principles of micro-RNA production and maturation.Oncogene.2006,25(45): 6156-6162.
6. Volk N, Shomron N. Versatility of MicroRNA Biogenesis. PLoS One 2011,6(5):el9391.
7. Zamore PD, Haley B. Ribo-gnome:the big world of small RNAs. Science 2005;309(5740):1519-1524.
8. Shin C, Nam JW, Farh KK, et al. Expanding the microRNA targeting code:functional sites with centered pairing. Mol Cell.2010,38(6):789-802.
9. Lai EC. MicroRNAs:runts of the genome assert themselves. Curr Biol 2003;13(23):925-936.
10. Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer,2006,6(4):259-269.
11. Hammond SM. MicroRNAs as tumor suppressors. Nat Genet 2007,39(5):582-583.
12. Brennecke J, Stark A, Russell RB,et al. Principles of microRNA-target recognition. PLoS Biol 2005,3(3):e85.
13. Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep.2006,16(4):845-850.
14. Takagi T, Iio A, Nakagawa Y, et al.Decreased expression of microRNA-143 and -145 in human gastric cancers. Oncology.2009,77(1):12-21.
15. Shi B, Sepp-Lorenzino L, Prisco M,et al. Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem.2007,282 (45):32582-32590.
16. Sachdeva M, Zhu S, Wu F, et al.p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA.2009,106(9):3207-3012.
17. Chen X, Gong J, Zeng H, et al. MicroRNA145 targets BNIP3 and suppresses prostate cancer progression. Cancer Res.2010,70(7):2728-2738.
18. Sachdeva M, Mo YY.et al.MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res.2010,70(1):378-387.
19. Yuan Z, Wong S, Borrelli A, et al. Down-regulation of MUC1 in cancer cells inhibits cell migration by promoting E-cadherin/catenin complex formation. Biochem Biophys Res Commun.2007,362(3):740-746.
20. Gotte M, Mohr C, Koo CY, et al. miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness. Oncogene.2010,29(50):6569-6580.
21. Arnaoutova I, George J, Kleinman HK, et al. The endothelial cell tube formation assay on basement membrane turns 20:state of the science and the art. Angiogenesis 2009,12(3):267-274.
22. Akao Y, Nakagawa Y, Naoe T. MicroRNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. Oncol Rep,2006,16(4):845-850.
23. La Rocca G, Shi B, Audia A, et al.Regulation of microRNA-145 by growth arrest and differentiation. Exp Cell Res.2011,317(4):488-495.
24. Riggi N, Suva ML, De Vito C, Provero P, Stehle JC, Baumer K, Cironi L,et al. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells.Genes Dev 2010;24:916-932.
25. Mohanraj D, Olson T, Ramakrishnan S.Expression of biologically active human vascular endothelial growth factor in yeast.Growth Factors.1995,12(l):17-27.
26. Jain L, Vargo CA, Danesi R, et al. The role of vascular endothelial growth factor SNPs as predictive and prognostic markers for major solid tumors.Mol Cancer Ther 2009,8(9):2496-2508.
27. Mei J, Gao Y, Zhang L,et al. VEGF-siRNA silencing induces apoptosis, inhibits proliferation and suppresses vasculogenic mimicry in osteosarcoma in vitro.Exp Oncol 2008,30(1):29-34.
28. Jung ST, Moon ES, Seo HY, Kim JS, Kim GJ, Kim YK. Expression and significance of TGF-beta isoform and VEGF in osteosarcoma.Orthopedics 2005,28(8):755-760.
29. Rennel E, Waine E, Guan H, et al.The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice.Br J Cancer 2008,98(7):1250-1257.
1. Ottaviani G, Jaffe N.The epidemiology of osteosarcoma. Cancer Treat Res. 2009,152:3-13. Review.
2.范磊,邵增务.小分子干扰RNA基因沉默与骨肉瘤治疗.国际骨科学杂志.2011,32(1)：30-32.
3. Mohanraj D, Olson T, Ramakrishnan S.Expression of biologically active human vascular endothelial growth factor in yeast.Growth Factors.1995,12(l):17-27.
4. Jain L, Vargo CA, Danesi R, et al. The role of vascular endothelial growth factor SNPs as predictive and prognostic markers for major solid tumors.Mol Cancer Ther 2009,8(9):2496-2508.
5. Mei J, Gao Y, Zhang L,et al. VEGF-siRNA silencing induces apoptosis, inhibits proliferation and suppresses vasculogenic mimicry in osteosarcoma in vitro.Exp Oncol 2008,30(1):29-34.
6. Jung ST, Moon ES, Seo HY, Kim JS, Kim GJ, Kim YK. Expression and significance of TGF-beta isoform and VEGF in osteosarcoma.Orthopedics 2005,28(8):755-760.
7. Rennel E, Waine E, Guan H, et al.The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice.Br J Cancer 2008,98(7):1250-1257.
8. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med.2006,355(24):2542-2550.
9. Zhong Hua, Qing Lv, Wenbin Ye, et al. MiRNA-Directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One.2006,1(1):e116.
10. Cheng Y, Liu X, Yang J, et al. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res. 2009,105(2):158-166.
11. Dallago CM, Oliveira MC, et al. Angiogenesis in craniopharyngiomas:Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin. Endocr Pathol.2005,16(4):355-362.
12. Avetisov SE, Mamikoian VR, Surguch BK,et al. Antiangiogenic therapy for choroidal neovascularization induced by age-related macular degeneration (preliminary communication).Vestn Oftalmol.2009,125(6):3-8.
13. Lin EY, Li JF, Bricard Qet al. Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages.Mol Oncol.2007,1(3):288-302.
1. Ottaviani G, Jaffe N.The epidemiology of osteosarcoma. Cancer Treat Res. 2009,152:3-13. Review.
2.范磊,邵增务.小分子干扰RNA基因沉默与骨肉瘤治疗.国际骨科学杂志.2011,32(1)：30-32.
3.范磊,吴强,魏玉龙,等.MicroRNA-145对骨肉瘤细胞增殖及凋亡的影响.中国癌症杂志.2012,22(4)：247-249.
4. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell 2004,116(2):281-297.
5. Zeng Y. Principles of micro-RNA production and maturation.Oncogene.2006,25(45): 6156-6162.
6. Volk N, Shomron N. Versatility of MicroRNA Biogenesis. PLoS One 2011,6(5):e19391.
7. Zamore PD, Haley B. Ribo-gnome:the big world of small RNAs. Science 2005;309(5740):1519-1524.
8. Shin C, Nam JW, Farh KK, et al. Expanding the microRNA targeting code:functional sites with centered pairing. Mol Cell.2010,38(6):789-802.
9. Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer,2006,6(4):259-269.
10. Hammond SM. MicroRNAs as tumor suppressors. Nat Genet 2007,39(5):582-583.
11. Brennecke J, Stark A, Russell RB,et al. Principles of microRNA-target recognition. PLoS Biol 2005,3(3):e85.
12. Wang X, Tang S, Le SY,et al.Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 2008,3(7):e2557.
13. Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep.2006,16(4):845-850.
14. Shi B, Sepp-Lorenzino L, Prisco M,et al. Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem.2007,282 (45):32582-32590.
15. Sachdeva M, Zhu S, Wu F, et al.p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA.2009,106(9):3207-3012.
16. Chen X, Gong J, Zeng H, et al. MicroRNA145 targets BNIP3 and suppresses prostate cancer progression. Cancer Res.2010,70(7):2728-2738.
17. Sachdeva M, Mo YY.et al.MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res.2010,70(1):378-387.
18.王家琪,高悠水,梅炯,等.Ad-VEGF-siRNA抑制荷人骨肉瘤裸鼠血管生成的形态学研究.2009,28(6)：581-586.
19. Fan L, Wu Q, Shao ZW,et al. MicroRNA-145 targets vascular endothelial growth factor and inhibits invasion and metastasis of osteosarcoma cells. Acta Biochim Biophys Sin. 2012,44(5):407-414.
20. Charity RM, Foukas AF, Deshmukh NS,et al.Vascular endothelial growth factor expression in osteosarcoma.Clin Orthop Relat Res,2006,448:193-198.
1. Ferrari S, Smeland S, Mercuri M, et al. Neoadjuvantchemo therapy with high dose ifosfamide, high do seme thotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity:a joint study by the Italian and Scandinavian Sarcoma Groups. J Clin Oncol,2005,23 (34):8845-8852.
2. Bacci G, Ferrari S, Mercuri M, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities in patients aged 41-60 years:outcome in 34 cases treated with adriamycin, cisplatinum and ifosfamide between 1984 and 1999. Acta Orthop.2007,78(3):377-384.
3.Chitwood DH, Timmermans MC.Small RNAs are on the move. Nature. 2010,467(7314):415-419.
4. A116 M, Kornblihtt AR. Gene silencing:small RNAs control RNA polymerase II elongation.Curr Biol.2010,20(17):R704-707.
5. Bosher JM, Labouesse M. RNA interference:genetic wand and genetic watchdog. Nat Cell Biol.2000,2(2):E31-36..
6. Morris KV, Chan SW, Jacobsen SE, et al. Small interfering RNA-induced transcriptional gene silencing in human cells. Science.2004,305(5688):1289-1292.
7. Gaglione M, Messere A. Recent progress in chemically modified siRNAs. Mini Rev Med Chem.2010,10(7):578-595.
8. McManus MT, Sharp PA. Gene silencing in mammals by small interfering RNAs. Nat Rev Genet.2002,3(10):737-747.
9. Dorsett Y, Tuschl T. siRNAs:applications in functional genomics and potential as therapeutics. Nat Rev Drug Discov.2004,3(4):318-329.
10. Gross A, McDonnell JM, Korsmeyer SJ. Bcl-2 family members and the mitochondria in apoptosis.Genes Dev.1999,13(15):1899-1911.
11. Adams JM, Cory S. The bcl-2 protein family:arbiers of cell survival. Science.281 (5381):1322-1326.
12. Kaseta MK, Khaldi L, Gomatos IP,et al. Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma. J Surg Oncol.2008,97(3):259-266.
13. Nedelcu T, Kubista B, Koller A, et al.Livin and Bcl-2 expression in high-grade osteosarcoma [J]. J Cancer Res Clin Oncol.2008,134(2):237-244.
14.龚旭,张玉诺,刘方欣,等.RNA干扰bcl-2基因对人骨肉瘤细胞株MG63增殖影响的实验研究.重庆医学.2009,38(4)：441-443.
15. Wang D, Liu M, Wang M, Zhang Y.Construction of recombinant adenovirus vector by c-myc silencing.Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi.2008,22(8):969-973.
16. Mirandola P, Sponzilli I, Gobbi G,et al.Anticancer agents sensitize osteosarcoma cells to TNF-related apoptosis-inducing ligand downmodulating IAP family proteins. Int J Oncol.2006,28(1):127-33.
17. Peng XH, Kama P, O'Regan RM,et al. Down-regulation of inhibitor of apoptosis proteins by deguelin selectively induces apoptosis in breast cancer cells. Mol Pharmacol. 2007,71 (1):101-111.
18. Esposito I, Kleeff J, Abiatari I,et al. Overexpression of cellular inhibitor of apoptosis protein 2 is an early event in the progression of pancreatic cancer.J Clin Pathol. 2007,60(8):885-95.
19. Ma O, Cai WW, Zender L, Dayaram T,et al. MMP13, Birc2 (cIAPl), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression. Cancer Res.2009,69(6):2559-2567.
20. Zaffaroni N, Pennati M, Daidone MG Survivin as a target for new anticancer interventions.:Cell Mol Med.2005,9(2):360-372.
21. Zhang HZ, Wang Y, Gao P,et al. Silencing stathmin gene expression by survivin promoter -driven siRNA vector to reverse malignant phenotype of tumor cells. Cancer Biol Ther.2006,5(11):1457-1461.
22. Fossey SL, Liao AT, McCleese JK, et al. Characterization of STAT3 activation and expression in canine and human osteosarcoma. MC Cancer.2009,9:81.
23. Weiss KR, Cooper GM, Jadlowiec JA, VEGF and BMP expression in mouse osteosarcoma cells. Clin Orthop Relat Res.2006,450:111-117.
24.丁勇,范德刚,单乐群.等.ShRNA表达载体干涉CyclinD1分子抑制骨肉瘤细胞系SOSP29607的增殖.2009,25(12)：1155-1157.
25. Liu Y, Ding JY, Shen WL,et al. Knockdown of cyclin A2 expression by small interfering RNA in MG-63 cells. Zhonghua Zhong Liu Za Zhi.2007,29(9):670-675.
26. Ek ET, Ojaimi J, Kitagawa Y, et al. Does the degree of intratumoural microvessel density and VEGF expression have prognostic significance in osteosarcoma? Oncol Rep. 2006,16(1):17-23.
27. Mei J, Gao Y, Zhang L, Cai X, et al. VEGF-siRNA silencing induces apoptosis, inhibits proliferation and suppresses vasculogenic mimicry in osteosarcoma in vitro. Exp Oncol.2008,30(1):29-34.
28.王家琪,高悠水,梅炯,等.Ad-VEGF-siRNA抑制荷人骨肉瘤裸鼠血管生成的形态学研究.癌症.2009,28(6)：581-586.
29. Zauli G, Rimondi E, Corallini F,et al. MDM2 antagonist Nutlin-3 suppresses the proliferation and differentiation of human pre-osteoclasts through a p53-dependent pathway. J Bone Miner Res.2007,22(10):1621-30.
30. Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol.2008,134(3):281-297.
31. Dass CR, Nadesapillai AP, Robin D,et al. Downregulation of uPAR confirms link in growth and metastasis of osteosarcoma.Clin Exp Metastasis.2005,22(8):643-652.
32. Khanna C, Wan X, Bose S, Cassaday R, et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med.2004,10(2):182-186. Epub 2004 Jan 4.
33. Kim C, Shin E, Hong S,et al.Clinical value of ezrin expression in primary osteosarcoma. Cancer Res Treat.2009,41(3):138-144.
1. Bielack SS, Kempf-Bielack B,et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk:an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocois.J Clin Oncol.2002,20(3):776-790.
2. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell. 2004,116(2):281-97.
3. Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer.2006,6(4):259-269.
4. Hammond SM. MicroRNAs as tumor suppressors. Nat Genet.2007,39(5):582-583.
5. Gregory RI, Shiekhatter R. MicroRNA biogenesis and cancer. Cancer Res,2005,65(9): 3509-3512.
6. Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5'UTR as in the 3'UTR.Proc Natl Acad Sci USA, 2007,104(23):9667-9672.
7. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.Cell.1993,75(5):843-854.
8. Berezikov E, Guryev V, van de Belt J,et al. Phylogenetic shadowing and computational identification of human microRNA genes.Cell.2005,120(1):21-24.
9. Croce CM. Causes and consequences of microRNA dysregulation in cancer.Nat Rev Genet.2009,10(10):704-714.
10. Kansara M, Thomas DM. Molecular pathogenesis of osteosarcoma.DNA Cell Biol. 2007,26(1):1-18.
11. Tang N, Song WX, Luo J,et al. Osteosarcoma development and stem cell differentiation.Clin Orthop Relat Res.2008,466(9):2114-2130.
12. Siclari VA, Qin L. Targeting the osteosarcoma cancer stem cell.J Orthop Surg Res. 2010,5:78.
13. Subramanian S, Lui WO, Lee CH,et al. MicroRNA expression signature of human sarcomas. Oncogene.2008,27(14):2015-2026.
14. Sarver AL, Phalak R, Thayanithy V,et al. S-MED:sarcoma microRNA expression database.Lab Invest.2010,90(5):753-761.
15. Liu C, Tang DG. MicroRNA regulation of cancer stem cells. Cancer Res.2011,71(18): 5950-5954.
16. Maire G, Martin JW, Yoshimoto M,et al. Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma.Cancer Genet.2011,204(3):138-146.
17. Lulla RR, Costa FF, Bischof JM,et al. Identification of Differentially Expressed MicroRNAs in Osteosarcoma. Sarcoma.2011,2011:732690.
18. Schaap-Oziemlak AM, Raymakers RA,et al. MicroRNA hsa-miR-135b regulates mineralization in osteogenic differentiation of human unrestricted somatic stem cells.Stem Cells Dev.2010,19(6):877-885.
19. L. Stabley, D. Kamara, J. Holbrook et al.Digital gene expression of mirna in osteosarcoma xenografts:finding biological relevance in mirna high throughput sequencing dataJournal of Biomolecular Techniques.2010,21(3):S25.
20.魏任雄,蔡林,谭金海,等.骨肉瘤miRNA基因的差异性表达.中华实验外科杂志,2009,26(5)：636-635.
21.高杰,杨彤涛,裘秀春,等.成骨肉瘤细胞SOSP-9607中miRNA的克隆与验证.癌症,2007,26(6)：561-565.
22.熊为,肖涛.实时荧光定量PCR检测骨肉瘤病人血清中microRNA的表达.中南大学硕士毕业论文.2010.
23. Marina N, Gebhardt M, Teot L,et al. Biology and therapeutic advances for pediatric osteosarcoma.Oncologist.2004,9(4):422-441.
24. Ta HT, Dass CR, Choong PF, et al. Osteosarcoma treatment:state of the art. Cancer Metastasis Rev.2009,28(1-2):247-263.
25. Hauben El, Arends J, Vandenbroucke JP,et al. Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma.Eur J Hum Genet.2003,11(8):611-618.
26. Hermeking H.The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010,17(2):193-199.
27. He C, Xiong J, Xu X,et al. Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples.Biochem Biophys Res Commun.2009,388(1):35-40.
28. Creighton CJ, Fountain MD, Yu Z,et al. Cancer Res. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.2010,70(5):1906-1915.
29. C. J. Braun, X. Zhang, I. Savelyeva et al., et al. p53-responsive microRNAs 192 and 215 are capable of inducing cell cycle arrest Cancer Research, 2008,68(24):10094-10104.
30. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells.Cancer Res.2005,65(14):6029-6033.
31.Meng F, Henson R, Wehbe-Janek H,et al. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer.Gastroenterology. 2007,133(2):647-658.
32. Asangani IA, Rasheed SA, Nikolova DA,et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer.Oncogene.2008,27(15):2128-2136.
33.Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem.2007,282(19):14328-14336.
34.吴子晏,刘小云,杨述华.miR-21对骨肉瘤细胞增殖的影响.中国癌症杂志,2010,20(8)：561-563.
35. Ziyan W, Shuhua Y, Xiufang W, et al. MicroRNA-21 is involvedin osteosarcoma cell invasion and migration. Med Oncol,2010,18(5):373-376.
36. Yuan J, Chen L, Chen X,et al. Identification of Serum MicroRNA-21 as a Biomarker for Chemosensitivity and Prognosis in Human Osteosarcoma.J Int Med Res. 2012;40(6):2090-2097.
37. Duan Z, Choy E, Harmon D,et al. MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther. 2011,10(8):1337-1345.
38. Osaki M, Takeshita F, Sugimoto Y,et al. MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression.Mol Ther. 2011,19(6):1123-1130.
39. Fan L, Wu Q, Xing X, et al. MicroRNA-145 targets vascular endothelial growth factor and inhibits invasion and metastasis of osteosarcoma cells.Acta Biochim Biophys Sin. 2012,44(5):407-414
40. Li Y, Zhang J, Si M,et al. Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of osteosarcoma cells by switching on suppressor microRNAs and inactivating of Notch-1 signaling.Carcinogenesis.2013.[Epub ahead of print]
41. Mao JH, Zhou RP, Peng AF,et al. microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN.Oncol Lett.2012,4(5):1125-1129.
42. Zhao G, Cai C, Yang T,et al. MicroRNA-221 Induces Cell Survival and Cisplatin Resistance through PI3K/Akt Pathway in Human Osteosarcoma. PLoS One. 2013,8(1):e53906.
43. Zhu J, Feng Y, Ke Z,et al. Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting Ezrin. Am J Pathol.2012,180(6):2440-2451.
44. Nana-Sinkam SP, Croce CM. MicroRNAs as therapeutic targets in cancer. Transl Res. 2011,157(4):216-225.
45. Pecot CV, Calin GA, Coleman RL,et al. RNA interference in the clinic:challenges and future directions. Nat Rev Cancer.2011,11(1):59-67.
46. Stegmeier F, Hu G, Rickles RJ,et al. A lentiviral microRNA-based system for single-copy polymerase II-regulated RNA interference in mammalian cells.Proc Natl Acad Sci USA.2005,102(37):13212-13217.
47. M. Osaki, F. Takeshita, Y. Sugimoto et al. MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression. Molecular Therapy.2011,19(6):1123-1130.
48. Y. Chen, X. Zhu, X. Zhang, et al. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy.Molecular Therapy.2010,18(9): 1650-1656.
2.范磊,邵增务.小分子干扰RNA基因沉默与骨肉瘤治疗.国际骨科学杂志.2011,32(1)：30-32.
3.范磊,吴强,魏玉龙,等.MicroRNA-145对骨肉瘤细胞增殖及凋亡的影响.中国癌症杂志.2012,22(4)：247-249.
4. Jeanteur P. miRNAs and cancer. Bull Cancer.2010,97(11):1231-1239.
5. Volk N, Shomron N. Versatility of MicroRNA Biogenesis. PLoS One 2011;6(5):e19391.
6. Wang X, Tang S, Le SY,et al.Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 2008,3(7):e2557.
7. Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep.2006,16(4):845-850.
8. Takagi T, Iio A, Nakagawa Y, et al.Decreased expression of microRNA-143 and-145 in human gastric cancers. Oncology.2009,77(1):12-21.
9. Anne Saaristo, Terhi Karpanen, Kari Alitalo. Mechanisms of angiogenesis and their use in the inhibition of tumor growth and metastasis.Oncogene.2000,19(53):6122-6129.
10. Mei J, Gao Y, Zhang L, Cai X,et al. VEGF-siRNA silencing induces apoptosis, inhibits proliferation and suppresses vasculogenic mimicry in osteosarcoma in vitro.Exp Oncol. 2008,30(1):29-34.
11. 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;25(4):402-408.
12. Calin GA, Sevignani C, Dumitru CD,et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA.2004,101(9):2999-3004.
13. Volpicelli P, Latagliata R, Carmosino I, et al. Familial occurrence of myelodysplastic syndrome with del(5q).Leuk Lymphoma.2011,52(6):1143-1145.
14. Sachdeva M, Mo YY. MiR-145-mediated suppression of cell growth, invasion and metastasis. Am J Transl Res.2010,2(2):170-180.
15. Sachdeva M, Mo YY. MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res.2010,70(1):378-387.
16. Shi B, Sepp-Lorenzino L, Prisco M,et al. MicroRNA-145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem.2007, 282(45):32582-32590.
17. Dallago CM, Oliveira MC, et al. Angiogenesis in craniopharyngiomas:Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin. Endocr Pathol.2005,16(4):355-362.
18. Avetisov SE, Mamikoian VR, Surguch BK,et al. Antiangiogenic therapy for choroidal neovascularization induced by age-related macular degeneration (preliminary communication). Vestn Oftalmol.2009,125(6):3-8.
19. Lin EY, Li JF, Bricard Qet al. Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages.Mol Oncol.2007,1(3):288-302.
1. Ottaviani G, Jaffe N.The epidemiology of osteosarcoma. Cancer Treat Res. 2009,152:3-13. Review.
2.范磊,邵增务.小分子干扰RNA基因沉默与骨肉瘤治疗.国际骨科学杂志.2011,32(1)：30-32.
3.范磊,吴强,魏玉龙,等.MicroRNA-145对骨肉瘤细胞增殖及凋亡的影响.中国癌症杂志.2012,22(4)：247-249.
4. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell 2004,116(2):281-297.
5. Zeng Y. Principles of micro-RNA production and maturation.Oncogene.2006,25(45): 6156-6162.
6. Volk N, Shomron N. Versatility of MicroRNA Biogenesis. PLoS One 2011,6(5):el9391.
7. Zamore PD, Haley B. Ribo-gnome:the big world of small RNAs. Science 2005;309(5740):1519-1524.
8. Shin C, Nam JW, Farh KK, et al. Expanding the microRNA targeting code:functional sites with centered pairing. Mol Cell.2010,38(6):789-802.
9. Lai EC. MicroRNAs:runts of the genome assert themselves. Curr Biol 2003;13(23):925-936.
10. Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer,2006,6(4):259-269.
11. Hammond SM. MicroRNAs as tumor suppressors. Nat Genet 2007,39(5):582-583.
12. Brennecke J, Stark A, Russell RB,et al. Principles of microRNA-target recognition. PLoS Biol 2005,3(3):e85.
13. Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep.2006,16(4):845-850.
14. Takagi T, Iio A, Nakagawa Y, et al.Decreased expression of microRNA-143 and -145 in human gastric cancers. Oncology.2009,77(1):12-21.
15. Shi B, Sepp-Lorenzino L, Prisco M,et al. Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem.2007,282 (45):32582-32590.
16. Sachdeva M, Zhu S, Wu F, et al.p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA.2009,106(9):3207-3012.
17. Chen X, Gong J, Zeng H, et al. MicroRNA145 targets BNIP3 and suppresses prostate cancer progression. Cancer Res.2010,70(7):2728-2738.
18. Sachdeva M, Mo YY.et al.MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res.2010,70(1):378-387.
19. Yuan Z, Wong S, Borrelli A, et al. Down-regulation of MUC1 in cancer cells inhibits cell migration by promoting E-cadherin/catenin complex formation. Biochem Biophys Res Commun.2007,362(3):740-746.
20. Gotte M, Mohr C, Koo CY, et al. miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness. Oncogene.2010,29(50):6569-6580.
21. Arnaoutova I, George J, Kleinman HK, et al. The endothelial cell tube formation assay on basement membrane turns 20:state of the science and the art. Angiogenesis 2009,12(3):267-274.
22. Akao Y, Nakagawa Y, Naoe T. MicroRNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. Oncol Rep,2006,16(4):845-850.
23. La Rocca G, Shi B, Audia A, et al.Regulation of microRNA-145 by growth arrest and differentiation. Exp Cell Res.2011,317(4):488-495.
24. Riggi N, Suva ML, De Vito C, Provero P, Stehle JC, Baumer K, Cironi L,et al. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells.Genes Dev 2010;24:916-932.
25. Mohanraj D, Olson T, Ramakrishnan S.Expression of biologically active human vascular endothelial growth factor in yeast.Growth Factors.1995,12(l):17-27.
26. Jain L, Vargo CA, Danesi R, et al. The role of vascular endothelial growth factor SNPs as predictive and prognostic markers for major solid tumors.Mol Cancer Ther 2009,8(9):2496-2508.
27. Mei J, Gao Y, Zhang L,et al. VEGF-siRNA silencing induces apoptosis, inhibits proliferation and suppresses vasculogenic mimicry in osteosarcoma in vitro.Exp Oncol 2008,30(1):29-34.
28. Jung ST, Moon ES, Seo HY, Kim JS, Kim GJ, Kim YK. Expression and significance of TGF-beta isoform and VEGF in osteosarcoma.Orthopedics 2005,28(8):755-760.
29. Rennel E, Waine E, Guan H, et al.The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice.Br J Cancer 2008,98(7):1250-1257.
1. Ottaviani G, Jaffe N.The epidemiology of osteosarcoma. Cancer Treat Res. 2009,152:3-13. Review.
2.范磊,邵增务.小分子干扰RNA基因沉默与骨肉瘤治疗.国际骨科学杂志.2011,32(1)：30-32.
3. Mohanraj D, Olson T, Ramakrishnan S.Expression of biologically active human vascular endothelial growth factor in yeast.Growth Factors.1995,12(l):17-27.
4. Jain L, Vargo CA, Danesi R, et al. The role of vascular endothelial growth factor SNPs as predictive and prognostic markers for major solid tumors.Mol Cancer Ther 2009,8(9):2496-2508.
5. Mei J, Gao Y, Zhang L,et al. VEGF-siRNA silencing induces apoptosis, inhibits proliferation and suppresses vasculogenic mimicry in osteosarcoma in vitro.Exp Oncol 2008,30(1):29-34.
6. Jung ST, Moon ES, Seo HY, Kim JS, Kim GJ, Kim YK. Expression and significance of TGF-beta isoform and VEGF in osteosarcoma.Orthopedics 2005,28(8):755-760.
7. Rennel E, Waine E, Guan H, et al.The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice.Br J Cancer 2008,98(7):1250-1257.
8. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med.2006,355(24):2542-2550.
9. Zhong Hua, Qing Lv, Wenbin Ye, et al. MiRNA-Directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One.2006,1(1):e116.
10. Cheng Y, Liu X, Yang J, et al. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res. 2009,105(2):158-166.
11. Dallago CM, Oliveira MC, et al. Angiogenesis in craniopharyngiomas:Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin. Endocr Pathol.2005,16(4):355-362.
12. Avetisov SE, Mamikoian VR, Surguch BK,et al. Antiangiogenic therapy for choroidal neovascularization induced by age-related macular degeneration (preliminary communication).Vestn Oftalmol.2009,125(6):3-8.
13. Lin EY, Li JF, Bricard Qet al. Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages.Mol Oncol.2007,1(3):288-302.
1. Ottaviani G, Jaffe N.The epidemiology of osteosarcoma. Cancer Treat Res. 2009,152:3-13. Review.
2.范磊,邵增务.小分子干扰RNA基因沉默与骨肉瘤治疗.国际骨科学杂志.2011,32(1)：30-32.
3.范磊,吴强,魏玉龙,等.MicroRNA-145对骨肉瘤细胞增殖及凋亡的影响.中国癌症杂志.2012,22(4)：247-249.
4. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell 2004,116(2):281-297.
5. Zeng Y. Principles of micro-RNA production and maturation.Oncogene.2006,25(45): 6156-6162.
6. Volk N, Shomron N. Versatility of MicroRNA Biogenesis. PLoS One 2011,6(5):e19391.
7. Zamore PD, Haley B. Ribo-gnome:the big world of small RNAs. Science 2005;309(5740):1519-1524.
8. Shin C, Nam JW, Farh KK, et al. Expanding the microRNA targeting code:functional sites with centered pairing. Mol Cell.2010,38(6):789-802.
9. Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer,2006,6(4):259-269.
10. Hammond SM. MicroRNAs as tumor suppressors. Nat Genet 2007,39(5):582-583.
11. Brennecke J, Stark A, Russell RB,et al. Principles of microRNA-target recognition. PLoS Biol 2005,3(3):e85.
12. Wang X, Tang S, Le SY,et al.Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 2008,3(7):e2557.
13. Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep.2006,16(4):845-850.
14. Shi B, Sepp-Lorenzino L, Prisco M,et al. Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem.2007,282 (45):32582-32590.
15. Sachdeva M, Zhu S, Wu F, et al.p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA.2009,106(9):3207-3012.
16. Chen X, Gong J, Zeng H, et al. MicroRNA145 targets BNIP3 and suppresses prostate cancer progression. Cancer Res.2010,70(7):2728-2738.
17. Sachdeva M, Mo YY.et al.MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res.2010,70(1):378-387.
18.王家琪,高悠水,梅炯,等.Ad-VEGF-siRNA抑制荷人骨肉瘤裸鼠血管生成的形态学研究.2009,28(6)：581-586.
19. Fan L, Wu Q, Shao ZW,et al. MicroRNA-145 targets vascular endothelial growth factor and inhibits invasion and metastasis of osteosarcoma cells. Acta Biochim Biophys Sin. 2012,44(5):407-414.
20. Charity RM, Foukas AF, Deshmukh NS,et al.Vascular endothelial growth factor expression in osteosarcoma.Clin Orthop Relat Res,2006,448:193-198.
1. Ferrari S, Smeland S, Mercuri M, et al. Neoadjuvantchemo therapy with high dose ifosfamide, high do seme thotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity:a joint study by the Italian and Scandinavian Sarcoma Groups. J Clin Oncol,2005,23 (34):8845-8852.
2. Bacci G, Ferrari S, Mercuri M, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities in patients aged 41-60 years:outcome in 34 cases treated with adriamycin, cisplatinum and ifosfamide between 1984 and 1999. Acta Orthop.2007,78(3):377-384.
3.Chitwood DH, Timmermans MC.Small RNAs are on the move. Nature. 2010,467(7314):415-419.
4. A116 M, Kornblihtt AR. Gene silencing:small RNAs control RNA polymerase II elongation.Curr Biol.2010,20(17):R704-707.
5. Bosher JM, Labouesse M. RNA interference:genetic wand and genetic watchdog. Nat Cell Biol.2000,2(2):E31-36..
6. Morris KV, Chan SW, Jacobsen SE, et al. Small interfering RNA-induced transcriptional gene silencing in human cells. Science.2004,305(5688):1289-1292.
7. Gaglione M, Messere A. Recent progress in chemically modified siRNAs. Mini Rev Med Chem.2010,10(7):578-595.
8. McManus MT, Sharp PA. Gene silencing in mammals by small interfering RNAs. Nat Rev Genet.2002,3(10):737-747.
9. Dorsett Y, Tuschl T. siRNAs:applications in functional genomics and potential as therapeutics. Nat Rev Drug Discov.2004,3(4):318-329.
10. Gross A, McDonnell JM, Korsmeyer SJ. Bcl-2 family members and the mitochondria in apoptosis.Genes Dev.1999,13(15):1899-1911.
11. Adams JM, Cory S. The bcl-2 protein family:arbiers of cell survival. Science.281 (5381):1322-1326.
12. Kaseta MK, Khaldi L, Gomatos IP,et al. Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma. J Surg Oncol.2008,97(3):259-266.
13. Nedelcu T, Kubista B, Koller A, et al.Livin and Bcl-2 expression in high-grade osteosarcoma [J]. J Cancer Res Clin Oncol.2008,134(2):237-244.
14.龚旭,张玉诺,刘方欣,等.RNA干扰bcl-2基因对人骨肉瘤细胞株MG63增殖影响的实验研究.重庆医学.2009,38(4)：441-443.
15. Wang D, Liu M, Wang M, Zhang Y.Construction of recombinant adenovirus vector by c-myc silencing.Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi.2008,22(8):969-973.
16. Mirandola P, Sponzilli I, Gobbi G,et al.Anticancer agents sensitize osteosarcoma cells to TNF-related apoptosis-inducing ligand downmodulating IAP family proteins. Int J Oncol.2006,28(1):127-33.
17. Peng XH, Kama P, O'Regan RM,et al. Down-regulation of inhibitor of apoptosis proteins by deguelin selectively induces apoptosis in breast cancer cells. Mol Pharmacol. 2007,71 (1):101-111.
18. Esposito I, Kleeff J, Abiatari I,et al. Overexpression of cellular inhibitor of apoptosis protein 2 is an early event in the progression of pancreatic cancer.J Clin Pathol. 2007,60(8):885-95.
19. Ma O, Cai WW, Zender L, Dayaram T,et al. MMP13, Birc2 (cIAPl), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression. Cancer Res.2009,69(6):2559-2567.
20. Zaffaroni N, Pennati M, Daidone MG Survivin as a target for new anticancer interventions.:Cell Mol Med.2005,9(2):360-372.
21. Zhang HZ, Wang Y, Gao P,et al. Silencing stathmin gene expression by survivin promoter -driven siRNA vector to reverse malignant phenotype of tumor cells. Cancer Biol Ther.2006,5(11):1457-1461.
22. Fossey SL, Liao AT, McCleese JK, et al. Characterization of STAT3 activation and expression in canine and human osteosarcoma. MC Cancer.2009,9:81.
23. Weiss KR, Cooper GM, Jadlowiec JA, VEGF and BMP expression in mouse osteosarcoma cells. Clin Orthop Relat Res.2006,450:111-117.
24.丁勇,范德刚,单乐群.等.ShRNA表达载体干涉CyclinD1分子抑制骨肉瘤细胞系SOSP29607的增殖.2009,25(12)：1155-1157.
25. Liu Y, Ding JY, Shen WL,et al. Knockdown of cyclin A2 expression by small interfering RNA in MG-63 cells. Zhonghua Zhong Liu Za Zhi.2007,29(9):670-675.
26. Ek ET, Ojaimi J, Kitagawa Y, et al. Does the degree of intratumoural microvessel density and VEGF expression have prognostic significance in osteosarcoma? Oncol Rep. 2006,16(1):17-23.
27. Mei J, Gao Y, Zhang L, Cai X, et al. VEGF-siRNA silencing induces apoptosis, inhibits proliferation and suppresses vasculogenic mimicry in osteosarcoma in vitro. Exp Oncol.2008,30(1):29-34.
28.王家琪,高悠水,梅炯,等.Ad-VEGF-siRNA抑制荷人骨肉瘤裸鼠血管生成的形态学研究.癌症.2009,28(6)：581-586.
29. Zauli G, Rimondi E, Corallini F,et al. MDM2 antagonist Nutlin-3 suppresses the proliferation and differentiation of human pre-osteoclasts through a p53-dependent pathway. J Bone Miner Res.2007,22(10):1621-30.
30. Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol.2008,134(3):281-297.
31. Dass CR, Nadesapillai AP, Robin D,et al. Downregulation of uPAR confirms link in growth and metastasis of osteosarcoma.Clin Exp Metastasis.2005,22(8):643-652.
32. Khanna C, Wan X, Bose S, Cassaday R, et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med.2004,10(2):182-186. Epub 2004 Jan 4.
33. Kim C, Shin E, Hong S,et al.Clinical value of ezrin expression in primary osteosarcoma. Cancer Res Treat.2009,41(3):138-144.
1. Bielack SS, Kempf-Bielack B,et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk:an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocois.J Clin Oncol.2002,20(3):776-790.
2. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell. 2004,116(2):281-97.
3. Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer.2006,6(4):259-269.
4. Hammond SM. MicroRNAs as tumor suppressors. Nat Genet.2007,39(5):582-583.
5. Gregory RI, Shiekhatter R. MicroRNA biogenesis and cancer. Cancer Res,2005,65(9): 3509-3512.
6. Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5'UTR as in the 3'UTR.Proc Natl Acad Sci USA, 2007,104(23):9667-9672.
7. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.Cell.1993,75(5):843-854.
8. Berezikov E, Guryev V, van de Belt J,et al. Phylogenetic shadowing and computational identification of human microRNA genes.Cell.2005,120(1):21-24.
9. Croce CM. Causes and consequences of microRNA dysregulation in cancer.Nat Rev Genet.2009,10(10):704-714.
10. Kansara M, Thomas DM. Molecular pathogenesis of osteosarcoma.DNA Cell Biol. 2007,26(1):1-18.
11. Tang N, Song WX, Luo J,et al. Osteosarcoma development and stem cell differentiation.Clin Orthop Relat Res.2008,466(9):2114-2130.
12. Siclari VA, Qin L. Targeting the osteosarcoma cancer stem cell.J Orthop Surg Res. 2010,5:78.
13. Subramanian S, Lui WO, Lee CH,et al. MicroRNA expression signature of human sarcomas. Oncogene.2008,27(14):2015-2026.
14. Sarver AL, Phalak R, Thayanithy V,et al. S-MED:sarcoma microRNA expression database.Lab Invest.2010,90(5):753-761.
15. Liu C, Tang DG. MicroRNA regulation of cancer stem cells. Cancer Res.2011,71(18): 5950-5954.
16. Maire G, Martin JW, Yoshimoto M,et al. Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma.Cancer Genet.2011,204(3):138-146.
17. Lulla RR, Costa FF, Bischof JM,et al. Identification of Differentially Expressed MicroRNAs in Osteosarcoma. Sarcoma.2011,2011:732690.
18. Schaap-Oziemlak AM, Raymakers RA,et al. MicroRNA hsa-miR-135b regulates mineralization in osteogenic differentiation of human unrestricted somatic stem cells.Stem Cells Dev.2010,19(6):877-885.
19. L. Stabley, D. Kamara, J. Holbrook et al.Digital gene expression of mirna in osteosarcoma xenografts:finding biological relevance in mirna high throughput sequencing dataJournal of Biomolecular Techniques.2010,21(3):S25.
20.魏任雄,蔡林,谭金海,等.骨肉瘤miRNA基因的差异性表达.中华实验外科杂志,2009,26(5)：636-635.
21.高杰,杨彤涛,裘秀春,等.成骨肉瘤细胞SOSP-9607中miRNA的克隆与验证.癌症,2007,26(6)：561-565.
22.熊为,肖涛.实时荧光定量PCR检测骨肉瘤病人血清中microRNA的表达.中南大学硕士毕业论文.2010.
23. Marina N, Gebhardt M, Teot L,et al. Biology and therapeutic advances for pediatric osteosarcoma.Oncologist.2004,9(4):422-441.
24. Ta HT, Dass CR, Choong PF, et al. Osteosarcoma treatment:state of the art. Cancer Metastasis Rev.2009,28(1-2):247-263.
25. Hauben El, Arends J, Vandenbroucke JP,et al. Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma.Eur J Hum Genet.2003,11(8):611-618.
26. Hermeking H.The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010,17(2):193-199.
27. He C, Xiong J, Xu X,et al. Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples.Biochem Biophys Res Commun.2009,388(1):35-40.
28. Creighton CJ, Fountain MD, Yu Z,et al. Cancer Res. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.2010,70(5):1906-1915.
29. C. J. Braun, X. Zhang, I. Savelyeva et al., et al. p53-responsive microRNAs 192 and 215 are capable of inducing cell cycle arrest Cancer Research, 2008,68(24):10094-10104.
30. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells.Cancer Res.2005,65(14):6029-6033.
31.Meng F, Henson R, Wehbe-Janek H,et al. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer.Gastroenterology. 2007,133(2):647-658.
32. Asangani IA, Rasheed SA, Nikolova DA,et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer.Oncogene.2008,27(15):2128-2136.
33.Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem.2007,282(19):14328-14336.
34.吴子晏,刘小云,杨述华.miR-21对骨肉瘤细胞增殖的影响.中国癌症杂志,2010,20(8)：561-563.
35. Ziyan W, Shuhua Y, Xiufang W, et al. MicroRNA-21 is involvedin osteosarcoma cell invasion and migration. Med Oncol,2010,18(5):373-376.
36. Yuan J, Chen L, Chen X,et al. Identification of Serum MicroRNA-21 as a Biomarker for Chemosensitivity and Prognosis in Human Osteosarcoma.J Int Med Res. 2012;40(6):2090-2097.
37. Duan Z, Choy E, Harmon D,et al. MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther. 2011,10(8):1337-1345.
38. Osaki M, Takeshita F, Sugimoto Y,et al. MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression.Mol Ther. 2011,19(6):1123-1130.
39. Fan L, Wu Q, Xing X, et al. MicroRNA-145 targets vascular endothelial growth factor and inhibits invasion and metastasis of osteosarcoma cells.Acta Biochim Biophys Sin. 2012,44(5):407-414
40. Li Y, Zhang J, Si M,et al. Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of osteosarcoma cells by switching on suppressor microRNAs and inactivating of Notch-1 signaling.Carcinogenesis.2013.[Epub ahead of print]
41. Mao JH, Zhou RP, Peng AF,et al. microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN.Oncol Lett.2012,4(5):1125-1129.
42. Zhao G, Cai C, Yang T,et al. MicroRNA-221 Induces Cell Survival and Cisplatin Resistance through PI3K/Akt Pathway in Human Osteosarcoma. PLoS One. 2013,8(1):e53906.
43. Zhu J, Feng Y, Ke Z,et al. Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting Ezrin. Am J Pathol.2012,180(6):2440-2451.
44. Nana-Sinkam SP, Croce CM. MicroRNAs as therapeutic targets in cancer. Transl Res. 2011,157(4):216-225.
45. Pecot CV, Calin GA, Coleman RL,et al. RNA interference in the clinic:challenges and future directions. Nat Rev Cancer.2011,11(1):59-67.
46. Stegmeier F, Hu G, Rickles RJ,et al. A lentiviral microRNA-based system for single-copy polymerase II-regulated RNA interference in mammalian cells.Proc Natl Acad Sci USA.2005,102(37):13212-13217.
47. M. Osaki, F. Takeshita, Y. Sugimoto et al. MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression. Molecular Therapy.2011,19(6):1123-1130.
48. Y. Chen, X. Zhu, X. Zhang, et al. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy.Molecular Therapy.2010,18(9): 1650-1656.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |