基于生物信息学分析的子宫内膜异位症miRNAmRNA调控网络的初步构建  

Construction of miRNA-mRNA regulatory network of endometriosis based on bioinformatic analysis

作　　者：姜丽 章蒙蒙 王思雪 曹乐 周雨馨 方小玲[1] Li Jiang;Meng-meng Zhang;Si-xue Wang;Le Cao;Yu-xin Zhou;Xiao-ling Fang(Department of Obstetrics and Gynecology,The Second Xiangya Hospital,Central South University,Changsha,Hunan 410011,China)

机构地区：[1]中南大学湘雅二医院妇产科,湖南长沙410011

出　　处：《中国现代医学杂志》2020年第9期1-7,共7页China Journal of Modern Medicine

基　　金：国家自然科学基金(No:81671437);湖南省科技研发重点项目(No:2016JC2049)。

摘　　要：目的用生物信息学分析方法初步构建子宫内膜异位症miRNA-mRNA的调控网络,探索其在子宫内膜异位症中的分子调控机制。方法从GEO下载数据集GSE7305,使用R语言软件对其进行差异表达基因分析。使用DAVID在线网站对获得的差异表达基因进行基因功能和KEGG信号通路富集分析。通过HMDD v3.0精准查询与子宫内膜异位症相关且经过验证(≥2次)的miRNA,并使用miRwalk 2.0数据库预测其靶基因。将预测的靶基因和GSE7305中的差异表达基因求得交集,获得miRNA和mRNA相互作用关系对。在Cytoscape v3.6.1中绘制miRNA-mRNA调控网络图,并运用CytoHubba插件进行核心mRNA及miRNA的筛选,构建相应的子网络。结果从GSE7305中共获得655个差异表达基因,其主要富集于补体信号通路、p53信号通路、细胞黏附相关信号通路中。成功构建子宫内膜异位症miRNA-mRNA分子调控网络,并筛选出核心mRNA和miRNA:hsa-miR-20a-5p、hsa-miR-141-3p、hsa-miR-200b-3p、hsa-miR-449b-3p属于高频下调表达的miRNA,且均可靶向作用于GATA6;高频上调表达的hsa-miR-125-5p可同时作用于PGR、ESR1,并下调两者表达水平。结论通过基因芯片分析和数据库挖掘方法构建miRNA-mRNA调控网络,为研究子宫内膜异位症发病机制、探索联合miRNA及其靶基因作为临床诊断标志物提供可靠的研究方向。Objective To construct regulatory network of dysregulated miRNAs and mRNAs in endometriosis and explore its molecular pathogenesis based on bioinformatic analysis.Methods GSE7305 was download from GEO and conducted with difference expression genes(DEGs)analysis using R software.Endometriosis-related miRNAs were obtained via HMDD V3.0 according to the reported frequency(≥2)and target mRNAs were predicted by miRwalk 2.0.These predicted target mRNAs were intersected with DEGs(|log2 FC|≥2,P≤0.05)in GSE7305 and upon a matching analysis,miRNA-mRNA interaction pairs were acquired.Finally,miRNA-mRNA regulatory network was mapped by Cytoscape software and plugin cytohubba was applied to screen hub miRNAs and mRNAs,resulting in corresponding subnetworks.Result Total of 655 DEGs were obtained from GSE 7305 and most of them were enriched in complement and coagulation cascades pathway,p53 signaling pathway,Cell adhesion molecules(CAMs)pathway.In the established miRNA-mRNA regulatory network,hub downregulated miRNAs including hsa-miR-20a-5p,hsa-miR-141-3p,hsa-miR-200b-3p,hsa-miR-449b-3p all could regulate target gene GATA6.In addition,hub upregulated miRNA hsa-miR-125-5p could downregulate PGR and ESR1.Conclusion Establishment of miRNA-mRNA regulatory network through chip analysis and database mining provided new sight for exploring molecular pathogenesis as well as a combined biomarker based on miRNA-mRNA pairs in endometriosis.

关 键 词：子宫内膜异位症 MIRNA 基因芯片 差异表达基因 调控网络 

分 类 号：R711.71[医药卫生—妇产科学]