hsa-miR-21的生物信息学特征分析
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摘要
目的:观察人消化道肿瘤细胞株hsa-miR-21表达水平,通过生物信息学预测hsa-miR-21的靶基因,进一步分析其潜在功能,为其后续功能研究提供依据。方法:应用实时荧光定量PCR技术检测人胃癌细胞株AGS、人胆管癌细胞株QBC939、人食管鳞状细胞癌细胞株ECA109以及正常人食管上皮细胞株Het-1A中hsa-miR-21表达水平;应用pubmed检索hsa-miR-21已知相关文献;应用miRbase和NCBI数据库分析hsa-miR-21序列保守性和所在基因组特征;应用TargetScan、PicTar及miRanda预测hsa-miR-21的靶基因,并对其进行功能富集分析和信号转导通路富集分析。结果:(1)AGS、QBC939细胞株中hsa-miR-21表达水平显著上调,明显高于Het-1A细胞;(2)已有研究证实hsa-miR-21与多种肿瘤相关;(3)miR-21在多个物种间具有序列保守性;(4)Hsa-miR-21靶基因主要参与转录调控、信号转导和Notch信号通路的正向调控等生物学过程,涉及Notch、细胞周期和轴突导向等信号转导通路。结论:hsa-miR-21可能通过调控多个信号通路参与消化道肿瘤的发病机制。
Objective: To investigate hsa-miR-21 expression levels in alimentary tract carcinoma and predict targets and functions of hsa-miR-21 by bioinformatic analysis for further study.Methods: The expression levels of hsa-miR-21 in AGS,QBC939,ECA109 and Het-1A cells lines were detected by the real-time quantitative PCR technology.The current studies of hsa-miR-21 were reviewed by pubmed.The sequence conservation and genome characteristics of hsa-miR-21 were analysed by miRbase database and NCBI.TargetScan,PicTar and miRanda were used to predict the target genes of hsa-miR-21.The functions of the target genes were predicted via Gene ontology(GO) analysis and Pathway analysis.Results: Hsa-miR-21 expression levels in AGS and QBC939 cells were significantly increased than that in Het-1A cells.Previous studies showed that hsa-miR-21 was related with several cancers.The sequence of miR-21 was conservative in more than one species.Gene ontology analysis showed that the target genes of hsa-miR-21 were enriched in regulation of transcription,signal transduction,positive regulation of Notch signaling pathway and other biological processes.The pathway analysis showed that the target genes mainly involved in Notch signaling pathway,Cell cycle and Axon guidance.Conclusion: Hsa-miR-21 might be involved in the pathophysiological mechanism of alimentary tract carcinoma by regulating various signaling pathway.
Objective: To investigate hsa-miR-21 expression levels in alimentary tract carcinoma and predict targets and functions of hsa-miR-21 by bioinformatic analysis for further study.Methods: The expression levels of hsa-miR-21 in AGS,QBC939,ECA109 and Het-1A cells lines were detected by the real-time quantitative PCR technology.The current studies of hsa-miR-21 were reviewed by pubmed.The sequence conservation and genome characteristics of hsa-miR-21 were analysed by miRbase database and NCBI.TargetScan,PicTar and miRanda were used to predict the target genes of hsa-miR-21.The functions of the target genes were predicted via Gene ontology(GO) analysis and Pathway analysis.Results: Hsa-miR-21 expression levels in AGS and QBC939 cells were significantly increased than that in Het-1A cells.Previous studies showed that hsa-miR-21 was related with several cancers.The sequence of miR-21 was conservative in more than one species.Gene ontology analysis showed that the target genes of hsa-miR-21 were enriched in regulation of transcription,signal transduction,positive regulation of Notch signaling pathway and other biological processes.The pathway analysis showed that the target genes mainly involved in Notch signaling pathway,Cell cycle and Axon guidance.Conclusion: Hsa-miR-21 might be involved in the pathophysiological mechanism of alimentary tract carcinoma by regulating various signaling pathway.
引文
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[6]ZHOU X,REN Y,MOORE L,et al.Downregulation of miR-21inhibits EGFR pathway and suppresses the growth of humanglioblastoma cells independent of PTEN status[J].Lab Invest,2010,90(2):144-155.
[7]ZHANG Z,LI Z,GAO C,et al.miR-21 plays a pivotal role ingastric cancer pathogenesis and progression[J].Lab Invest,2008,88(12):1358-1366.
[8]ZHOU J,WANG K C,WU W,et al.MicroRNA-21 targets per-oxisome proliferators-activated receptor-alpha in an autoregula-tory loop to modulate flow-induced endothelial inflammation[J].Proc Natl Acad Sci U S A,2011,108(25):10355-10360.
[9]GABRIELY G,WURDINGER T,KESARI S,et al.MicroRNA21 promotes glioma invasion by targeting matrix metalloprotein-ase regulators[J].Mol Cell Biol,2008,28(17):5369-5380.
[10]ZHU S,SI M L,WU H,et al.MicroRNA-21 targets the tumorsuppressor gene tropomyosin 1(TPM1)[J].J Biol Chem,2007,282(19):14328-14336.
[11]WANG K,LI P F.Foxo3a regulates apoptosis by negativelytargeting miR-21[J].J Biol Chem,2010,285(22):16958-16966.
[12]KIM Y J,HWANG S J,BAE Y C,et al.MiR-21 regulates adi-pogenic differentiation through the modulation of TGF-betasignaling in mesenchymal stem cells derived from human adi-pose tissue[J].Stem Cells,2009,27(12):3093-3102.
[13]ZHU S,WU H,WU F,et al.MicroRNA-21 targets tumor sup-pressor genes in invasion and metastasis[J].Cell Res,2008,18(3):350-359.
[14]ZHENG J,XUE H,WANG T,et al.miR-21 downregulates thetumor suppressor P12 CDK2AP1 and stimulates cell prolifera-tion and invasion[J].J Cell Biochem,2011,112(3):872-880.
[15]王旭辉,陈明.miRNA和前列腺癌发生发展的关系[J].东南大学学报:医学版,2012,31(4):512-515.
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[17]FU X,HAN Y,WU Y,et al.Prognostic role of microRNA-21in various carcinomas:a systematic review and meta-analysis[J].Eur J Clin Invest,2011,41(11):1245-1253.