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

Objective To establish a microRNA-mRNA differential expression network for alcoholic hepatitis ( AH) , and to investigatenew targets for the diagnosis and treatment of AH. Methods Differentially expressed microRNAs and mRNAs between AH patients and nor-mal controls were screened out. Related software including TargetScan, DIANA, MIRDB, PICTAR, and miRWalk 2. 0 was used to searchfor the target genes of differentially expressed microRNA, and a key microRNA-mRNA network was established using the differentially ex-pressed mRNAs that changed in an opposite way to microRNA. The Database for Annotation, Visualization and Integrated Discovery wasused for the gene ontology ( GO) and Kyoto Encyclopedia of Genes and Genome ( KEGG) analyses of target genes. The GCBI online soft-ware ( www. gcbi. com. cn) was used for enrichment analysis of target genes and core network establishment. The GeneMANIA database inCytoscape software ( genemania. org) was used to perform a protein-protein interaction analysis of key target genes. The above three meth-ods were compared in terms of the search for key pathways involved in the development of AH. Results A key microRNA-mRNA networkwas established with 5 differentially expressed microRNAs including hsa-mir-21-5 p, hsa-mir-148 a-3 p, and hsa-mir-30 e-5 pand 51 target genes including collagen type IV alpha 1 chain ( COL4 A1) , thrombospondin-2 ( THBS2) , and integrin alpha 6 ( IGTA6) . Aprotein-protein interaction network of key target genes was established. The GO analysis and various pathway analyses showed that the PI3 K-Akt pathway and local adhesion were closely associated with AH. Conclusion During the development of AH, there are complex interac-tions between the related proteins of key target genes. COL4 A1 and THBS2 may promote the development of AH by activating ITGA6 to regu-late the PI3 K-Akt pathway and the process of local adhesion. The establishment of the microRNA-mRNA network reveals the key links inthe development of AH and highlights the focus of research. The discovery of the genes associated with the PI3 K-Akt pathway in AH is ex-pected to provide new targets for the diagnosis and treatment of AH.