酒精性肝炎microRNA-mRNA差异表达网络的生物信息学分析

目的构建酒精性肝炎(AH)的microRNA-mRNA差异表达网络,寻找AH新的诊疗靶标。方法筛选AH差异表达的microRNA和mRNA;基于TargetScan、DIANA、MIRDB、PICTAR、miRWalk2. 0等软件寻找差异microRNA靶基因,选取差异mRNA中与microRNA变化方向相反的靶基因,构建关键microRNA-mRNA网络;通过注释、可视化和集成发现数据库(DAVID)对相关靶基因进行基因本体论(GO)分析、京都基因与基因组百科全书数据库(KEGG)通路分析;通过GCBI (www. gcbi. com. cn)在线软件对靶基因进行疾病富集分析和核心网络构建;通过Cytoscape软件中GeneMANIA数据库(genemania. org)对关键靶基因进行蛋白相互作用分析,对比3种方法通路分析寻找AH发生过程中的关键通路。结果构建以hsa-mir-21-5p、hsa-mir-148a-3p和hsa-mir-30e-5p等5个差异microRNA及Ⅳ胶原α1链(COL4A1)、血栓反应素2(THBS2)和整合素亚单位α6(ITGA6)等51个靶基因为主体的AH关键microRNA-mRNA网络;构建关键靶基因相关的蛋白相互作用网络; GO分析和各种通路分析分析显示,磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)通路和局部黏附等过程与AH密切相关。结论 AH发病过程中,多种关键靶基因相关蛋白存在复杂的相互作用,COL4A1和THBS2可能通过激活ITGA6调节PI3K-Akt通路和局部黏附等过程,促进AH的发展; microRNA-mRNA网络的构建揭示了AH发生过程中的关键环节,凸显了研究重点,尤其是PI3K-Akt相关基因在AH中的发现,有望为AH的诊疗提供新的靶标。

A bioinformatics analysis of the microRNA-mRNA differential expression network for alcoholic hepatitis

ObjectiveTo establish a microRNA-mRNA differential expression network for alcoholic hepatitis (AH), and to investigate new targets for the diagnosis and treatment of AH. MethodsDifferentially expressed microRNAs and mRNAs between AH patients and normal controls were screened out. Related software including TargetScan, DIANA, MIRDB, PICTAR, and miRWalk 2.0 was used to search for the target genes of differentially expressed microRNA, and a key microRNA-mRNA network was established using the differentially expressed mRNAs that changed in an opposite way to microRNA. The Database for Annotation, Visualization and Integrated Discovery was used for the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses of target genes. The GCBI online software (www.gcbi.com.cn) was used for enrichment analysis of target genes and core network establishment. The GeneMANIA database in Cytoscape software (genemania.org) was used to perform a protein-protein interaction analysis of key target genes. The above three methods were compared in terms of the search for key pathways involved in the development of AH. ResultsA key microRNA-mRNA network was established with 5 differentially expressed microRNAs including hsa-mir-21-5p, hsa-mir-148a-3p, and hsa-mir-30e-5p and 51 target genes including collagen type IV alpha 1 chain (COL4A1), thrombospondin-2 (THBS2), and integrin alpha 6 (IGTA6). A protein-protein interaction network of key target genes was established. The GO analysis and various pathway analyses showed that the PI3K-Akt pathway and local adhesion were closely associated with AH. ConclusionDuring the development of AH, there are complex interactions between the related proteins of key target genes. COL4A1 and THBS2 may promote the development of AH by activating ITGA6 to regulate the PI3K-Akt pathway and the process of local adhesion. The establishment of the microRNA-mRNA network reveals the key links in the development of AH and highlights the focus of research. The discovery of the genes associated with the PI3K-Akt pathway in AH is expected to provide new targets for the diagnosis and treatment of AH.