Analysis of the value and possible mechanisms of miRNA in cirrhosis based on bioinformatics approach

Abstract Aim: Cirrhosis is the ultimate fate of several liver diseases, but the mechanisms regarding the development of cirrhosis remain unclear. In this study, we performed a screening of differentially expressed miRNAs in cirrhosis using public databases and explored their functions and pathways associated with cirrhosis.Methods: We screened differentially expressed miRNAs in cirrhosis using the GEO dataset and bioinformatics methods. in addition, we explored their possible biological pathways using analysis of differentially expressed miRNAs and their predicted target genes and gene ontology (GO) terms. The screened miRNAs were also validated.Results: In total, we screened out 129 differentially expressed miRNAs. The differentially expressed miRANs and their target genes are concentrated in the nucleus and cytoplasm, while their functions and pathways are closely related to the activities of transcription factors or related enzymes. We found that the main upstream transcription factors regulating differential miRNAs are SP1, SP4, KLF7, EGR1, POU2F1, and RREB1. Then, we combined two factors, top ranking and high repetition frequency, to derive the top three most important genes (CTNNB1, RHOA, RAC1). Finally, we also performed a ROC curve analysis of the diagnostic efficacy of has-miR-199a/b-3p for cirrhosis (Area under the curve=0.7531, Sensitivity=55.56% Specificity=100%).Conclusions: We screened for differentially expressed miRNAs in cirrhosis and analyzed their associated transcription factors and target genes. The differentially expressed miRNAs functioned in close correlation with the associated transcription factor activity. And, we identified the top three pivotal genes (CTNNB1, RHOA, RAC1) among the target genes. Finally, has-miR-199a/b-3p was analyzed and concluded that it can be used as a non-invasive diagnostic biomarker for liver cirrhosis. The differential miRNAs and their target genes identified in this study not only reveal new insights into the pathogenesis of cirrhosis, but also provide many potential targets for the treatment of cirrhosis.