FAM201A, a Long Noncoding RNA Potentially Associated With Atrial Fibrillation Identified by ceRNA Network Analyses and WGCNA

Abstract

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia that contributes to various complications. However, little is known about lncRNAs associated with AF susceptibility. In the present study, we aim to identify lncRNAs involved in pathogenesis of AF based on competing endogenous RNA (ceRNA) network analyses and weighted gene co-expression network analysis (WGCNA).Methods: Two lncRNA and mRNA microarray datasets GSE41177 and GSE79768 were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs) between AF patients and patients with sinus rhythm (SR) were identified from dataset GSE41177. Then, those DElncRNAs associated target miRNAs were predicted. The ceRNA network was constructed based on DElncRNAs, predicted miRNAs and DEmRNAs. To validate the role of AF-related lncRNAs, all lncRNAs form dataset GSE79768 were selected to perform WGCNA. LncRNA modules relevant to AF were identified. Crucial lncRNAs in the module that was most relevant to AF were screened according to the criteria of | Gene significance (GS)| > 0.6 and |Module membership (MM)| > 0.5. Results: A total of 18 DElncRNAs and 350 DEmRNAs were identified between AF patients and SR patients. The final ceRNA network contained 5 lncRNAs, 10 miRNAs, and 21 mRNAs. According to the ceRNA theory, combined with the comparative toxicogenomics database (CTD) database, the ceRNA axis FAM201A-miR-33a-3p-RAC3 was considered associated with AF susceptibility. By WGCNA, the blue module was detected most highly relevant with AF. The lncRNA FAM201A was proved in the blue module and highly related to AF. Conclusions: These results demonstrated that FAM201A might have great potential for susceptibility of AF based on ceRNA network analyses and WGCNA. FAM201A may function, at least partly, as ceRNA to regulate RAC3 in AF susceptibility.