异位子宫内膜组织差异miRNAs的生物信息学分析  

Bioinformatics analysis of differential miRNAs in ectopic endometrial tissues

作　　者：马兰芳 曹莉莉 吴章颖 汪俊涛[1] MA Lanfang;CAO Lili;WU Zhangying;WANG Juntao(Department of Obstetrics and Gynecology,Guiyang Maternity and Child Health Care Hospital,Guizhou Province,Guiyang550001,China;Department of Obstetrics and Gynecology,the Affiliated Hospital of Guizhou Medical University,Guizhou Province,Guiyang550003,China)

机构地区：[1]贵阳市妇幼保健院妇产科,贵州贵阳550001 [2]贵州医科大学附属医院妇产科,贵州贵阳550003

出　　处：《中国医药导报》2021年第36期81-84,90,F0004,共6页China Medical Herald

基　　金：国家自然科学基金资助项目(81760266)。

摘　　要：目的基于生物信息学分析,探索微RNA(miRNA)及其靶基因调控网络在子宫内膜异位症中的分子调控机制,为研究发病机制及治疗靶点提供新思路。方法从公共基因芯片数据库GEO下载关于异位内膜和在位内膜组织miRNA表达的数据集GSE105765,使用R语言软件对其差异表达的miRNA进行分析,并筛选出差异表达排名前6位的miRNA,利用在线数据库TargetScan、miRWalk和miRDB分别预测其靶基因,获得3个数据库同时预测的靶基因交集。使用DAVID在线网站对获得的交集靶基因通过GO和KEGG进行基因富集分析,以判定靶基因主要影响的生物学功能或通路。通过STRING数据库和Cytoscape软件对筛选得到的靶基因进行蛋白质-蛋白质相互作用(PPI)网络分析。结果筛选出异位内膜和在位内膜组织差异表达的miRNA共85个,其中排名前6位的是miR-202-5p、miR-514a-3p、miR-615-3p、miR-202-3p、miR-509-3p、miR-509-3-5p;3个数据库分别预测的靶基因交集有43、194、2、598、209、556个;GO和KEGG富集分析显示,6个miRNAs的交集靶基因与轴突转运、糖代谢代谢途径等密切相关;通过PPI网络和模块分析筛选出RAC1、EP300、EGFR、CTNNB1处于PPI核心位点。结论利用生物信息学发现,与在位内膜组织比较,异位内膜组织存在miRNA的差异表达,并通过靶基因参与调控轴突转运及糖代谢途径,为子宫内膜异位症的发病机制及治疗靶点研究提供了新证据。Objective To explore the molecular regulation mechanism of microRNA(miRNA)and its target gene regulatory network in endometriosis(endometriosis)based on bioinformatics analysis,and provide new ideas for the study of pathogenesis and therapeutic targets.Methods Data set GSE105765 on miRNA expression in ectopic endometrial and situ endometrial tissues was downloaded from the public gene chip database GEO,R language software was used to analyze the differentially expressed miRNA and screen out the top six miRNA with differentially expressed miRNA,target genes were predicted by online databases TargetScan,miRWalk,and miRDB,respectively,and the intersection of target genes predicted by the three databases was obtained.DAVID online website was used to conduct gene enrichment analysis for the intersection target genes obtained by GO and KEGG,so as to determine the biological function or pathway that the target genes mainly affect.Protein-protein interaction(PPI)network analysis was performed on the target genes screened by STRING database and Cytoscape software.Results A total of 85 miRNAs with difference expression in ectopic endometrial and situ endometrial tissues were screened out,among which the top six were miR-202-5p,miR-514a-3p,miR-615-3p,miR-202-3p,miR-509-3p,and miR-509-3-5p;there were 43,194,2,598,209,556 target gene intersections predicted by three databases;GO and KEGG enrichment analysis showed that the intersection target genes of six miRNAs were closely related to axon transport and glucose metabolism;through PPI network and module analysis,RAC1,EP300,EGFR,and CTNNB1 were screened as the core sites of protein interaction.Conclusion Using bioinformatics found that,compared with in situ endometrial tissues,miRNAs are differentially expressed in ectopic endometrial tissues,and target genes are involved in the regulation of axonal transport and glucose metabolism,providing new evidence for the pathogenesis and therapeutic target of endometriosis.

关 键 词：生物信息学 子宫内膜异位症 微RNA 靶基因 

分 类 号：R711.71[医药卫生—妇产科学]