原发性干燥综合征患者唾液腺组织ceRNA调控网络的构建

Construction and analysis of ceRNA network in salivary gland tissues of patients with primary Sjogren’s syndrome

目的通过生物信息学方法构建原发性干燥综合征(primary Sjögren’s syndrome,pSS)患者唾液腺组织中的竞争内源性RNA(competing endogenous RNA,ceRNA)调控网络并探讨其发病机制。方法利用基因表达综合数据库(Gene Expression Omnibus,GEO)对pSS患者唾液腺组织中的信使RNA(messenger RNA,mRNA)、长链非编码RNA(long non-coding RNA,lncRNA)表达谱作差异分析。通过miRcode数据库和3个miRNA数据库(TargetScan、miRDB和miRWalk)获取与pSS有关的靶微小RNA(microRNA,miRNA)和靶mRNA,构建lncRNA-miRNA-mRNA的ceRNA调控网络,对ceRNA网络中差异表达基因(differentially expressed mRNAs,DEmRNAs)进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。结果在ceRNA网络中有214个DEmRNAs。KEGG分析显示DEmRNAs的主要富集信号通路为丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路和腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)信号通路,DEmRNAs中10个枢纽(Hub)基因分别为JUN、CCND1、NRAS、DDX5、KAT2B、VEGFA、SIRT1、CLTA、MCM7和RPS6KA1。结论本研究通过构建ceRNA调控网络,发现网络中DEmRNAs主要富集MAPK和AMPK信号通路,为进一步深入探讨原发性干燥综合征的诊断和治疗提供了新的思路。

Objective The competing endogenous RNAs(ceRNA)regulation network in salivary gland tissues of patients with primary Sjögren’s syndrome(pSS)was constructed by bioinformatics methods and its pathogenesis was investigated.Methods Differential expression analyses of messenger RNA(mRNA)dataset and long non-coding RNA(lncRNA)dataset from salivary gland tissues of pSS patients were conducted based on GEO database.Target miRNA and target mRNA related to pSS were obtained through miRNA databases,and then lncRNA-miRNA-mRNA ceRNA regulation network was constructed.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed for differentially expressed mRNAs(DEmRNAs)in the ceRNA regulation network.Results A total of 214 target mRNA were obtained in the ceRNA network.KEGG analysis of different genes in the network showed that the main gene enrichment pathway were mitogen-activated protein kinase(MAPK)signaling pathway and AMP-activated protein kinase(AMPK)signaling pathway.Hub gene JUN,CCND1,NRAS,DDX5,KAT2B,VEGFA,SIRT1,CLTA,MCM7 and RPS6KA1 were selected in pSS.Conclusion This study finds that the DEmRNAs in the ceRNA regulatory network mainly enriched in MAPK and AMPK signaling pathways,which provided a new idea for the diagnosis and treatment of primary Sjogren’s syndrome.