外泌体lncRNA研究进展及其肿瘤靶向潜质（英文）
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摘要
外泌体和长链非编码RNA(lncRNA)与肿瘤等危害人类健康重大疾病的发生发展密切相关。对外泌体中lncRNA研究的深入解析有助于人们更加全面地了解癌症发生发展机理机制,并有助于为进一步肿瘤精准靶向治疗提供新的潜在标志物及临床靶点。本综述阐述了外泌体的发生过程及其内容lncRNA,并进一步通过深入总结外泌体lncRNA在肿瘤临床药物耐受中的作用,评估其肿瘤靶向潜质,揭示其作为潜在有效靶向治疗靶点和诊疗标志物的前景意义。
Exosomes and long non-coding RNAs(lncRNAs) are emerging as important elements contributing to a more comprehensive understanding of cancer development and progression. The discovery of lncRNAs in exosomes further indicates their bona fide biological functional roles in cancer development and drug resistance. In this review, we describe the biogenesis of exosomes and summarize the function of exosomal lncRNAs in the field of cancer research. These findings strikingly advance current knowledge of exosomal lncRNAs and suggest that they may be promising diagnostic biomarkers and therapeutic targets for cancer.
Exosomes and long non-coding RNAs(lncRNAs) are emerging as important elements contributing to a more comprehensive understanding of cancer development and progression. The discovery of lncRNAs in exosomes further indicates their bona fide biological functional roles in cancer development and drug resistance. In this review, we describe the biogenesis of exosomes and summarize the function of exosomal lncRNAs in the field of cancer research. These findings strikingly advance current knowledge of exosomal lncRNAs and suggest that they may be promising diagnostic biomarkers and therapeutic targets for cancer.
引文
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Hessvik NP,Llorente A,2018.Current knowledge on exosome biogenesis and release.Cell Mol Life Sci,75(2):193-208.https://doi.org/10.1007/s00018-017-2595-9
Hoshino A,Costa-Silva B,Shen TL,et al.,2015.Tumour exosome integrins determine organotropic metastasis.Nature,527(7578):329-335.https://doi.org/10.1038/nature15756
Juan T,Fürthauer M,2017.Biogenesis and function of ESCRT-dependent extracellular vesicles.Semin Cell Dev Biol,74:66-77.https://doi.org/10.1016/j.semcdb.2017.08.022
Kang M,Ren MP,Li Y,et al.,2018.Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA.J Exp Clin Cancer Res,37:171.https://doi.org/10.1186/s13046-018-0845-9
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Ohya T,Miaczynska M,Coskunü,et al.,2009.Reconstitution of Rab-and SNARE-dependent membrane fusion by synthetic endosomes.Nature,459(7250):1091-1097.https://doi.org/10.1038/nature08107
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Piper RC,Katzmann DJ,2007.Biogenesis and function of multivesicular bodies.Annu Rev Cell Dev Biol,23:519-547.https://doi.org/10.1146/annurev.cellbio.23.090506.123319
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Shao HL,Im H,Castro CM,et al.,2018.New technologies for analysis of extracellular vesicles.Chem Rev,118(4):1917-1950.https://doi.org/10.1021/acs.chemrev.7b00534
Soysal SD,Tzankov A,Muenst SE,2015.Role of the tumor microenvironment in breast cancer.Pathobiology,82(3-4):142-152.https://doi.org/10.1159/000430499
Takahashi K,Yan IK,Kogure T,et al.,2014a.Extracellular vesicle-mediated transfer of long non-coding RNA RORmodulates chemosensitivity in human hepatocellular cancer.FEBS Open Bio,4:458-467.https://doi.org/10.1016/j.fob.2014.04.007
Takahashi K,Yan IK,Wood J,et al.,2014b.Involvement of extracellular vesicle long noncoding RNA(linc-VLDLR)in tumor cell responses to chemotherapy.Mol Cancer Res,12(10):1377-1387.https://doi.org/10.1158/1541-7786.MCR-13-0636
Tamai K,Tanaka N,Nakano T,et al.,2010.Exosome secretion of dendritic cells is regulated by Hrs,an ESCRT-0 protein.Biochem Biophys Res Commun,399(3):384-390.https://doi.org/10.1016/j.bbrc.2010.07.083
Tan SK,Pastori C,Penas C,et al.,2018.Serum long noncoding RNA HOTAIR as a novel diagnostic and prognostic biomarker in glioblastoma multiforme.Mol Cancer,17:74.https://doi.org/10.1186/s12943-018-0822-0
Tang JW,Jiang RQ,Deng L,et al.,2015.Circulation long non-coding RNAs act as biomarkers for predicting tumorigenesis and metastasis in hepatocellular carcinoma.Oncotarget,6(6):4505-4515.https://doi.org/10.18632/oncotarget.2934
Théry C,Zitvogel L,Amigorena S,2002.Exosomes:composition,biogenesis and function.Nat Rev Immunol,2(8):569-579.https://doi.org/10.1038/nri855
Trajkovic K,Hsu C,Chiantia S,et al.,2008.Ceramide triggers budding of exosome vesicles into multivesicular endosomes.Science,319(5867):1244-1247.https://doi.org/10.1126/science.1153124
Valadi H,Ekstr?m K,Bossios A,et al.,2007.Exosomemediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.Nat Cell Biol,9(6):654-659.https://doi.org/10.1038/ncb1596
Villarroya-Beltri C,Baixauli F,Mittelbrunn M,et al.,2016.ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins.Nat Commun,7:13588.https://doi.org/10.1038/ncomms13588
Wang JT,Zhou YD,Lu JG,et al.,2014.Combined detection of serum exosomal mi R-21 and HOTAIR as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma.Med Oncol,31(9):148.https://doi.org/10.1007/s12032-014-0148-8
Zeigerer A,Gilleron J,Bogorad RL,et al.,2012.Rab5 is necessary for the biogenesis of the endolysosomal system in vivo.Nature,485(7399):465-470.https://doi.org/10.1038/nature11133
Zhang W,Cai XR,Yu J,et al.,2018.Exosome-mediated transfer of lncRNA RP11-838N2.4 promotes erlotinib resistance in non-small cell lung cancer.Int J Oncol,53(2):527-538.https://doi.org/10.3892/ijo.2018.4412
Zhao R,Zhang YL,Zhang X,et al.,2018.Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer.Mol Cancer,17(1):68.https://doi.org/10.1186/s12943-018-0817-x
Zheng X,Han H,Liu GP,et al.,2017.Lnc RNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism.EMBO J,36(22):3325-3335.https://doi.org/10.15252/embj.201797609
Zhou RH,Chen KK,Zhang JT,et al.,2018.The decade of exosomal long RNA species:an emerging cancer antagonist.Mol Cancer,17:75.https://doi.org/10.1186/s12943-018-0823-z
Berrondo C,Flax J,Kucherov V,et al.,2016.Expression of the long non-coding RNA HOTAIR correlates with disease progression in bladder cancer and is contained in bladder cancer patient urinary exosomes.PLoS ONE,11(1):e0147236.https://doi.org/10.1371/journal.pone.0147236
Bunggulawa EJ,Wang W,Yin TY,et al.,2018.Recent advancements in the use of exosomes as drug delivery systems.J Nanobiotechnol,16(1):81.https://doi.org/10.1186/s12951-018-0403-9
Chairoungdua A,Smith DL,Pochard P,et al.,2010.Exosome release ofβ-catenin:a novel mechanism that antagonizes Wnt signaling.J Cell Biol,190(6):1079-1091.https://doi.org/10.1083/jcb.201002049
Dai MY,Chen XL,Mo SY,et al.,2017.Meta-signature lncRNAs serve as novel biomarkers for colorectal cancer:integrated bioinformatics analysis,experimental validation and diagnostic evaluation.Sci Rep,7:46572.https://doi.org/10.1038/srep46572
Dong HY,Wang W,Chen R,et al.,2018.Exosome-mediated transfer of lncRNA-SNHG14 promotes trastuzumab chemoresistance in breast cancer.Int J Oncol,53(3):1013-1026.https://doi.org/10.3892/ijo.2018.4467
Hessvik NP,Llorente A,2018.Current knowledge on exosome biogenesis and release.Cell Mol Life Sci,75(2):193-208.https://doi.org/10.1007/s00018-017-2595-9
Hoshino A,Costa-Silva B,Shen TL,et al.,2015.Tumour exosome integrins determine organotropic metastasis.Nature,527(7578):329-335.https://doi.org/10.1038/nature15756
Juan T,Fürthauer M,2017.Biogenesis and function of ESCRT-dependent extracellular vesicles.Semin Cell Dev Biol,74:66-77.https://doi.org/10.1016/j.semcdb.2017.08.022
Kang M,Ren MP,Li Y,et al.,2018.Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA.J Exp Clin Cancer Res,37:171.https://doi.org/10.1186/s13046-018-0845-9
Li BG,Mao R,Liu CF,et al.,2018.LncRNA FAL1 promotes cell proliferation and migration by acting as a ceRNA of miR-1236 in hepatocellular carcinoma cells.Life Sci,197:122-129.https://doi.org/10.1016/j.lfs.2018.02.006
Li Q,Huang QP,Wang YL,et al.,2018.Extracellular vesiclemediated bone metabolism in the bone microenvironment.J Bone Miner Metab,36(1):1-11.https://doi.org/10.1007/s00774-017-0860-5
Ma YX,Zhang JM,Wen LX,et al.,2018.Membrane-lipid associated lncRNA:a new regulator in cancer signaling.Cancer Lett,419:27-29.https://doi.org/10.1016/j.canlet.2018.01.008
Matsumoto A,Takahashi Y,Nishikawa M,et al.,2017.Role of phosphatidylserine-derived negative surface charges in the recognition and uptake of intravenously injected B16BL6-derived exosomes by macrophages.J Pharm Sci,106(1):168-175.https://doi.org/10.1016/j.xphs.2016.07.022
Melo SA,Luecke LB,Kahlert C,et al.,2015.Glypican-1identifies cancer exosomes and detects early pancreatic cancer.Nature,523(7559):177-182.https://doi.org/10.1038/nature14581
Ohya T,Miaczynska M,Coskunü,et al.,2009.Reconstitution of Rab-and SNARE-dependent membrane fusion by synthetic endosomes.Nature,459(7250):1091-1097.https://doi.org/10.1038/nature08107
Ostrowski M,Carmo NB,Krumeich S,et al.,2010.Rab27a and Rab27b control different steps of the exosome secretion pathway.Nat Cell Biol,12(1):19-30.https://doi.org/10.1038/ncb2000
Park O,Choi ES,Yu GH,et al.,2018.Efficient delivery of tyrosinase related protein-2(TRP2)peptides to lymph nodes using serum-derived exosomes.Macromol Biosci,18(12):1800301.https://doi.org/10.1002/mabi.201800301
Piper RC,Katzmann DJ,2007.Biogenesis and function of multivesicular bodies.Annu Rev Cell Dev Biol,23:519-547.https://doi.org/10.1146/annurev.cellbio.23.090506.123319
Qu L,Ding J,Chen C,et al.,2016.Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA.Cancer Cell,29(5):653-668.https://doi.org/10.1016/j.ccell.2016.03.004
Sang LJ,Ju HQ,Liu GP,et al.,2018.LncRNA CamK-A regulates Ca2+-signaling-mediated tumor microenvironment remodeling.Mol Cell,72(1):71-83.e7.https://doi.org/10.1016/j.molcel.2018.08.014
Shao HL,Im H,Castro CM,et al.,2018.New technologies for analysis of extracellular vesicles.Chem Rev,118(4):1917-1950.https://doi.org/10.1021/acs.chemrev.7b00534
Soysal SD,Tzankov A,Muenst SE,2015.Role of the tumor microenvironment in breast cancer.Pathobiology,82(3-4):142-152.https://doi.org/10.1159/000430499
Takahashi K,Yan IK,Kogure T,et al.,2014a.Extracellular vesicle-mediated transfer of long non-coding RNA RORmodulates chemosensitivity in human hepatocellular cancer.FEBS Open Bio,4:458-467.https://doi.org/10.1016/j.fob.2014.04.007
Takahashi K,Yan IK,Wood J,et al.,2014b.Involvement of extracellular vesicle long noncoding RNA(linc-VLDLR)in tumor cell responses to chemotherapy.Mol Cancer Res,12(10):1377-1387.https://doi.org/10.1158/1541-7786.MCR-13-0636
Tamai K,Tanaka N,Nakano T,et al.,2010.Exosome secretion of dendritic cells is regulated by Hrs,an ESCRT-0 protein.Biochem Biophys Res Commun,399(3):384-390.https://doi.org/10.1016/j.bbrc.2010.07.083
Tan SK,Pastori C,Penas C,et al.,2018.Serum long noncoding RNA HOTAIR as a novel diagnostic and prognostic biomarker in glioblastoma multiforme.Mol Cancer,17:74.https://doi.org/10.1186/s12943-018-0822-0
Tang JW,Jiang RQ,Deng L,et al.,2015.Circulation long non-coding RNAs act as biomarkers for predicting tumorigenesis and metastasis in hepatocellular carcinoma.Oncotarget,6(6):4505-4515.https://doi.org/10.18632/oncotarget.2934
Théry C,Zitvogel L,Amigorena S,2002.Exosomes:composition,biogenesis and function.Nat Rev Immunol,2(8):569-579.https://doi.org/10.1038/nri855
Trajkovic K,Hsu C,Chiantia S,et al.,2008.Ceramide triggers budding of exosome vesicles into multivesicular endosomes.Science,319(5867):1244-1247.https://doi.org/10.1126/science.1153124
Valadi H,Ekstr?m K,Bossios A,et al.,2007.Exosomemediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.Nat Cell Biol,9(6):654-659.https://doi.org/10.1038/ncb1596
Villarroya-Beltri C,Baixauli F,Mittelbrunn M,et al.,2016.ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins.Nat Commun,7:13588.https://doi.org/10.1038/ncomms13588
Wang JT,Zhou YD,Lu JG,et al.,2014.Combined detection of serum exosomal mi R-21 and HOTAIR as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma.Med Oncol,31(9):148.https://doi.org/10.1007/s12032-014-0148-8
Zeigerer A,Gilleron J,Bogorad RL,et al.,2012.Rab5 is necessary for the biogenesis of the endolysosomal system in vivo.Nature,485(7399):465-470.https://doi.org/10.1038/nature11133
Zhang W,Cai XR,Yu J,et al.,2018.Exosome-mediated transfer of lncRNA RP11-838N2.4 promotes erlotinib resistance in non-small cell lung cancer.Int J Oncol,53(2):527-538.https://doi.org/10.3892/ijo.2018.4412
Zhao R,Zhang YL,Zhang X,et al.,2018.Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer.Mol Cancer,17(1):68.https://doi.org/10.1186/s12943-018-0817-x
Zheng X,Han H,Liu GP,et al.,2017.Lnc RNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism.EMBO J,36(22):3325-3335.https://doi.org/10.15252/embj.201797609
Zhou RH,Chen KK,Zhang JT,et al.,2018.The decade of exosomal long RNA species:an emerging cancer antagonist.Mol Cancer,17:75.https://doi.org/10.1186/s12943-018-0823-z