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人microRNA-200家族靶基因预测及生物信息学分析
张英,秦江月,贾慧卓,陈磊,申永春,文富强
0
(四川大学华西医院呼吸与危重症医学科·生物治疗国家重点实验室呼吸病学研究室)
摘要:
【摘要】 目的 对microRNA200(miR200)家族成员的靶基因进行预测和生物信息学分析,为进一步探讨miR200家族的功能及其调节机制提供证据。方法 运用靶基因预测软件TargetScan、PicTar2和miRanda分别预测miR200家族9个成员的靶基因,再分别取各自在三个软件下预测所得靶基因的交集,然后利用miRTarbase数据库获取这9个miRNA经过至少3种实验验证并且靶向关系类型为具有功能的miRNA靶基因互作的靶基因,将软件预测所得结果与靶向关系预测结果取并集,作为所纳入每个miRNA的靶基因集合,然后分别对靶基因集合进行生物学过程的功能富集,信号通路及蛋白质互作网络分析。结果 miR-200家族的预测靶基因富集于多个生物学过程,其生物学过程主要富集于:RNA聚合酶Ⅱ启动子的转录负调控、DNA模板转录负调控、RNA聚合酶Ⅱ启动子的转录调控等;信号通路主要富集于:肿瘤、胶质瘤、黑色素瘤、肺小细胞癌等多种肿瘤和EB病毒感染、乙型肝炎等感染相关通路,蛋白质互作网络显示9个成员的预测靶基因编码蛋白质间存在复杂的相互作用,靶基因编码蛋白质“RAC1”、“SRC”、“RHOA”、“CREBBP”、“CTNNB1”在互作网络中具有核心地位。结论200家族中的成员通过调控靶基因进而调节下游靶蛋白参与肿瘤、感染等病理生理进程。
关键词:  microRNA-200家族  靶基因  生物信息学  互作网络  信号通路
DOI:
基金项目:国家自然科学基金面上项目
Target gene prediction and bioinformatics analysis of human microRNA 200 family
ZHANG Ying,QIN Jiangyue,JIA Huizhuo,CHEN Lei,SHEN Yongchun,WEN Fuqiang
(Department of Respiratory and Critical Care Medicine, Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital)
Abstract:
【Abstract】 Objective The target genes of miRNA 200 family members were predicted and bioinformatics analyzed to provide evidence for further study of the function and regulatory mechanism of miRNA 200 family. Methods Target Scan, PicTar2 and Miranda were used to predict the target genes of the nine members of miR200 family, and then the intersection of the predicted target genes was obtained. Target genes were also predicted by miRTarbase, which were validated by at least three experiments and the type of targeting relationship was functional microRNAtarget gene interaction. The final target genes were combined with the results of Target Scan, PicTar2, Miranda, and miRTarbase. Bioinformatics function analysis including GeneOntology analysis, signal pathway analysis, and proteinprotein interaction (PPI) networks analysis were performed. Results The predicted target genes of miR 200 family were enriched in many biological processes, which were mainly enriched in transcriptional negative regulation of RNA polymerase Ⅱ promoter, DNA template transcriptional negative regulation, transcriptional regulation of RNA polymerase Ⅱ promoter, etc. The signal pathway was mainly enriched in tumor, glioma, melanoma, small cell lung cancer and other tumors, and infection related pathways such as EB virus infection and hepatitis B. The protein interaction network shown that there were complex interactions among the predicted target gene coding proteins of 9 members, and the target gene coding proteins "Rac1", "SRC", "RhoA", "crebbp" and "CTNNB1" played a key role in the interaction network. Conclusion Members of the Mir 200 family participate in the pathophysiological process of tumor and infection by regulating the target gene and then regulating the downstream target protein; Interaction pathway; Signal path
Key words:  miR-200 family  Target genes  Bioinformatics analysis  Interaction pathway  Signal path

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