Identification of Pivotal MicroRNAs and Target Genes Associated with Persistent Atrial Fibrillation Based on Bioinformatics Analysis

Abstract

Atrial fibrillation (AF) is one of the most common supraventricular arrhythmias worldwide. However, the specific molecular mechanism underlying AF remains unclear. Our study is aimed at identifying pivotal microRNAs (miRNAs) and targeting genes associated with persistent AF (pAF) using bioinformatics analysis. Three gene expression array datasets (GSE31821, GSE41177, and GSE79768) and an miRNA expression array dataset (GSE68475) associated with pAF were downloaded. Differentially expressed genes (DEGs) were identified using the LIMMA package, and differentially expressed miRNAs (DEMs) were screened from GSE68475. Target genes for DEMs were predicted using the miRTarBase database, and intersections between these target genes and DEGs were selected for further analysis, including the generation of protein-protein interaction (PPI) network, miRNA-transcription factor-target regulatory network, and drug-gene network. A total of 264 DEGs and 40 DEMs were identified between the pAF and control groups. Functional and pathway enrichment analyses of up- and downregulated DEGs were performed. The common genes (CGs) were primarily enriched in the phosphoinositide 3-kinase- (PI3K-) protein kinase B (Akt) signaling pathway, negative regulation of cell division, and response to hypoxia. The PPI network, miRNA-transcription factor-target regulatory network, and drug-gene network were constructed using Cytoscape. The present study revealed several novel miRNAs and genes involved in pAF. We speculated that miR-4298, miR-3125, miR-4306, and miR-671-5p could represent significant miRNAs that act on the target gene superoxide dismutase 2 (SOD2) during the development of pAF and may serve as essential biomarkers for pAF diagnosis and treatment. Moreover, MYC might function in pAF pathogenesis through the PI3K-Akt signaling pathway.