基于生物信息学的胰岛素分泌细胞诱导分化早期转录因子-微小RNA-mRNA调控网络的构建  

Construction of transcription factor⁃microRNA⁃mRNA regulatory network during the induction of insulin⁃producing cells by bioinformatics methods

作　　者：王涛 赵雨薇 潘鑫 马云胜 WANG Tao;ZHAO Yu-wei;PAN Xin;MA Yun-sheng(Department of Medicine of Medical Treatment College,Liaoning Jinzhou Medical University,Liaoning Jinzhou 121013,China;Medical Radiologic Technology of Medical Treatment College,Liaoning Jinzhou Medical University,Liaoning Jinzhou 121013,China)

机构地区：[1]锦州医科大学医疗学院医学系,辽宁锦州121013 [2]锦州医科大学医疗学院医学技术系,辽宁锦州121013

出　　处：《解剖学报》2025年第1期80-87,共8页Acta Anatomica Sinica

基　　金：国家级大学生创新创业训练项目(202313213002);辽宁省教育厅高校基本科研项目(LJKMZ20222086)。

摘　　要：目的探讨人胚胎干细胞(hESCs)向胰岛素分泌细胞(IPCs)诱导分化前期差异表达的基因(DEGs)并构建微小RNA(miRNA)-mRNA调控网络。方法选择基因表达综合数据库(GEO)内的GSE42094数据集作为研究对象,分为hESCs、Diff1、Diff2、Diff3、Diff4和IPCs 6组。选取Diff1组一过性表达DEGs,进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)路径显著性分析,选用STRING数据库进行蛋白相互作用网络分析,运用miRTarBase数据库预测其靶miRNA,构建miRNA-mRNA调控网络并可视化,应用文献数据进行验证。结果GO功能和KEGG路径显著性分析发现,Diff1组28个DEGs在生物学过程方面主要集中在原胚肠形成中的细胞迁移和SMAD蛋白信号转导,涉及的KEGG路径为转化生长因子β(TGF-β)和干细胞多能性调控信号通路。通过miRTarBase数据库查找靶miRNA,发现miR-335-5p能够调控CDA、IFITM1、FREM1、FGF17和ROR25个基因的表达。进一步通过文献数据验证,发现有26个miRNA存在于hESCs向IPCs诱导分化的过程中。结论靶向一过性表达DEGs的miRNA参与IPCs诱导分化进程,其miRNA-mRNA调控网络在诱导分化早期起重要作用。Objective To identify differentially expressed genes(DEGs)during the early stage of differentiation of human embryonic stem cells(hESCs)into insulin⁃producing cells(IPCs)and construct the microRNA(miRNA)⁃mRNA regulatory network.Methods The datasets GSE42094 from Gene Expression Omnibus(GEO)were employed in this study and included hESCs,Diff1,Diff2,Diff3,Diff4 and IPCs groups.DEGs in the Diff1 group were selected and gene ontology(GO)and Keyoto Encyclopedia of Genes and Genomes(KEGG)pathway were deciphered.The miRNAs associated with DEGs were predicted and the miRNA⁃mRNA regulatory network was visualized.Then the predicted miRNA was validated by paper result.Results GO result demonstrated that the significant term of biological process were“cell migration involved in gastrulation”and“SMAD protein signal transduction”.The KEGG pathway analysis indicated that“transformating growth factor(TGF)⁃beta signaling pathway”and“Signaling pathways regulating pluripotency of stem cells”played essential roles for 28 DEGs in the Diff1 group.To predict miRNA associated with DEGs,we found that miR⁃335⁃5p may regulate expressions of CDA,IFITM1,FREM1,FGF17 and ROR2 genes.There were 26 miRNAs which were validated by result of paper.Conclusion The miRNA⁃mRNA regulatory network plays an essential role during the early stage of the induction of IPCs.

关 键 词：微小RNA 人胚胎干细胞 胰岛素分泌细胞 生物信息学 

分 类 号：R34[医药卫生—基础医学]