Bioinformatics analysis of differential expression genes and microRNA-messenger RNA regulatory network in biliary atresia / 中华实用儿科临床杂志

ABSTRACT

Objective:To mining differential expression genes (DEGs) and establish a regulatory network of dysregulated microRNAs (miRNAs) and messenger RNAs (mRNAs) in biliary atresia (BA) spectrum via bioinforma-tics analysis, and to explore the pathogenesis of BA.Methods:GSE46960 dataset was download from gene expression omnibus (GEO). DEGs between normal liver tissues and BA tissues were analyzed using the GEO2R analysis tool.The functional and pathway enrichment analyses of DEGs were performed utilizing the Database for Annotation, Visualization and Integrated Discovery (DAVID6.8). A protein-protein interaction (PPI) network was constructed using the PPI database (STRING11.0) and Cytoscape_v3.7.1 software, and thus key genes were analyzed.BA-related miRNAs were obtained using the human miRNA disease database (HMDD_V3.0) and target mRNAs were predicted by the miRNA target prediction database (miRDB). The intersection between the predicted target mRNAs and DEGs from the GSE46960 dataset was selected.The regulatory network of miRNA-mRNA was constructed using Cytoscape software.Results:A total of 565 DEGs, including 352 up-regulated ones and 213 down-regulated ones were identified.Among them, up-regulated DEGs were enriched in extracellular matrix(ECM)-receptor interaction, focal adhesion kinase (FAK), Amoebiasis, and the phosphoinositide 3 kinase/protein kinase B(PI3K/Akt) pathway.Down-regulated DEGs were enriched in metabolic signaling, biosynthesis of antibiotics and steroid biosynthesis pathway.From the PPI network, 10 key genes were screened out.A complex miRNA-mRNA regulatory network was constructed based on screened DEGs.Conclusions:Identified DEGs and miRNA-mRNA regulatory network constructed in this study may help clarify the molecular mechanisms of BA.This study provides a new direction to explore promising molecular targets for the diagnosis and treatment of BA.