不明原因复发性流产患者胎盘绒毛组织差异表达miRNA的生物信息学分析

Bioinformatics analysis of differentially expressed miRNA in placental villi of patients with unexplained recurrent spontaneous abortion

目的对不明原因复发性流产(URSA)患者胎盘绒毛组织差异表达miRNA的靶基因进行生物信息学分析,并构建miRNA调控网络,为后续的机制研究及临床治疗提供理论基础及新思路。方法在数据库GEO中选择URSA患者胎盘组织miRNA差异表达数据集GSE73025,应用GEO2R软件处理并筛选差异表达miRNA;利用在线分析网站miRDB、TargetScan及miRTarBase软件预测靶基因,并对其进行生物信息学分析;利用SRTING网站及Cytoscape软件构建miRNA调控网络。结果共筛选出54个差异表达miRNAs,其中上调35个,下调19个;上调幅度最大的3个miRNA分别为miR-4497、miR-149-3p及miR-1469;下调幅度最大的3个miRNA分别为miR-614、miR-548aa及miR-363-5p。对上述miRNAs靶基因进行KEGG信号通路富集分析,显示其靶基因在Wnt/β-catenin信号通路、TLR4信号通路及Tim-3/Gal-9信号通路中富集程度最高。通过构建miRNA-mRNA调控网络图可知上调组中3个miRNA均处于调控网络的中心位置,且以miR-4497为核心;同时多个靶基因受多个miRNA的共同作用,其核心基因为IGF-1R、MMP2及GBX2。下调组miRNA调控网络图中可发现miR-614及miR-363-5p调控大多数Hub基因,同时其核心基因为DKK1。结论筛选出miRNA及核心基因可为后续的靶基因验证及机制研究提供理论基础和研究思路,生物信息学分析在探索生物机理方面具有可靠性。

Objective Bioinformatics analysis of the target genes of differentially expressed miRNAs in placental villi of patients with unexplained recurrent spontaneous abortion(URSA), and construction of a miRNA regulatory network.Methods Select the data set GSE73025 of miRNA differential expression in placental tissues of URSA patients in the database GEO, and use GEO2 R software to process and screen differentially expressed miRNAs. Use online analysis websites miRDB,TargetScan and miRTarBase software to predict target genes, and conduct bioinformatics analysis on them, and construct miRNA-mRNA regulatory network. Results A total of 54 differentially expressed miRNAs were screened, of which 35 were up-regulated and 19 were down-regulated. The three miRNAs with the largest up-regulation were miR-4497, miR-149-3 p and miR-1469;the three miRNAs with the largest down-regulation were miR-614, miR-548 aa and miR-363-5 p. Enrichment analysis of KEGG signaling pathway found that the target gene was most enriched in Wnt/β-catenin signaling pathway, TLR4 signaling pathway and Tim-3/Gal-9 signaling pathway. The three miRNAs in the up-regulated group are all at the center of the regulatory network, with miR-4497 as the core, and its core genes are IGF-1 R, MMP2 and GBX2. In the down-regulated group,miR-614 and miR-363-5 p regulate most of the Hub genes, and the core gene is DKK1. Conclusion Screening out miRNAs and core genes can provide theoretical basis and research ideas for subsequent target gene verification and mechanism research.