胰岛素分泌细胞诱导过程中miRNA-mRNA调控网络的生物信息学分析

Bioinformatic Analyses of miRNA-mRNA Regulatory Network During Differentiation of Insulin-producing Cells

目的探讨人胚胎干细胞(hESCs)向胰岛素分泌细胞(IPCs)诱导分化过程中基因表达的差异,并构建miRNA-mRNA调控网络。方法选择GEO数据库内的GSE42094数据集作为研究对象,应用GEO2R分析差异表达基因,对其进行GO功能和KEGG路径以及蛋白互作网络分析,选用miRTarBase数据库预测其靶miRNA,对miRNA-mRNA调控网络进行可视化,并采用文献数据验证。结果共得到差异表达基因188个,选取诱导后显著下调基因共21个,分析发现POU5F1、DNMT3B和NANOG 3个基因集中在“基因表达调控”,且下调基因在“胞核内”比较集中;通过查找靶miRNA,发现miR-335-5p能够调控POU5F1、DNMT3B、NANOG、FAM124B和LECT15个基因的表达;验证发现有24个miRNA能够被文献数据验证。结论基于显著下调基因构建的miRNA-mRNA调控网络参与干细胞诱导分化进程并发挥重要作用。

Objective To identify differentially expressed genes during differentiation of human embryonic stem cells(hESCs)into insulin-producing cells,and to construct the miRNA-mRNA regulatory network.Methods The datasets GSE42094 from GEO were employed in this study,differentially expressed genes were analyzed using GEO2R,and the GO function,KEGG pathway and protein interaction network were analyzed.The miRTarBase database was used to predict its target miRNA,and the miRNA-mRNA regulatory network was visualized and verified by literature data.Results A total of 188 differentially expressed genes were identified and 21 down-regulated genes after the induction were selected as candidate genes.POU5F1,DNMT3B and NANOG were"regulation of gene expression"and the significant term for all down-regulated genes were"nucleus".By searching for target miRNAs,it was found that miR-335-5p could regulate the expression of POU5F1,DNMT3B,NANOG,FAM124B and LECT1;validation found that 24 miRNAs could be verified by literature data.Conclusion The miRNA-mRNA regulatory network based on down-regulated genes may play a key role during induction of insulin-producing cells.