基于生物信息学方法的2型糖尿病差异表达miRNA筛选及靶基因预测

Screening of differentially expressed miRNA and prediction of target genes in type 2 diabetes based on bioinformatics

目的基于生物信息学方法分析2型糖尿病(T2DM)患者肝脏组织中差异miRNA表达,并预测靶基因。方法通过GEO数据库下载T2DM与正常人群肝脏组织miRNA芯片数据集GSE176025,分为type-2-dabetic和non-diabetic两组,每组20例,利用GEOR2工具分析获取差异miRNA,并制作火山图。通过TargetScan和miRWalk数据库对差异miRNA行靶基因预测,并利用DAVID数据库对靶基因从生物过程(BP)、细胞成分(CC)、分子功能(MF)做基因本体论功能富集分析(GO)和京都基因组百科全书信号通路分析(KEGG)。利用STRING在线工具及Cytoscape软件构建靶基因蛋白质相互作用(PPI)网络,并筛选关键基因。结果筛选后获得差异miRNA 15个,包含12个上调miRNA和3个下调miRNA。预测差异miRNA靶基因318个,关键靶基因5个,分别为SMARCD3、BCL11A、BCL11B、ARID2、BICRA。GO及KEGG分析结果显示,BP包括调控RNA聚合酶Ⅱ启动子转录、DNA模板转录、蛋白质磷酸化等;CC包括细胞核、核质、细胞质、细胞溶质等;MF包括蛋白质结合、DNA结合、染色质结合等;KEGG包括调节干细胞多能性的信号通路、mTOR信号通路、Hippo信号通路等。结论与正常人群相比,T2DM患者肝脏组织中存在多个差异miRNA表达;这些差异miRNA及相关靶基因等有助于明确T2DM发病机制,为临床诊疗提供新的思路。

Objective To analyze differential miRNA expression and target gene prediction in liver tissues of patients with type 2 diabetes mellitus(T2DM)by bioinformatics method.Methods The liver tissue miRNA chip dataset GSE176025 of T2DM and normal population was downloaded from GEO database,including type-2-dabetic and non-diabetic groups,with 20 cases in each group.The GEO R2 tool was used to analyze and obtain the differential miRNA,and a volcano map was made.Target genes of differential miRNA were predicted by TargetScan and miRWalk databases.Gene ontological functional enrichment analysis(GO)and Kyoto Genome Encyclopedia Signaling Pathway Analysis(KEGG)were performed on target genes from biological process(BP),cell component(CC)and molecular function(MF)using DAVID database.The STRING online tool and Cytoscape software were used to construct a PPI network of target genes,and key genes were screened.Results A total of 15 differential miRNAs were selected,including 12 up-regulated miR⁃NAs and 3 down-regulated miRNAs.A total of 318 target genes were predicted for differential miRNAs,and 5 key target genes were identified,namely SMARCD3,BCL11A,BCL11B,ARID2,and BICRA.GO and KEGG analysis showed that BP included regulation of transcription from RNA polymerase Ⅱ promoter,DNA-templated transcription,protein phos⁃phorylation and so on;CC included nucleus,nucleolus,cytoplasm,cytoplasm and so on;MF included protein binding,DNA binding,chromatin binding and so on;KEGG included signaling pathways regulating pluripotency of stem cells,mTOR signaling pathway,Hippo signaling pathway and so on.Conclusions Compared with the normal population,there are several different miRNA expressions in liver tissues of T2DM patients.These differential miRNAs and their target genes may help to clarify the pathogenesis of T2DM and provide new ideas for clinical diagnosis and treatment.