FAM201A, a long noncoding RNA potentially associated with atrial fibrillation identified by ceRNA network analyses and WGCNA

Abstract

Background Being the most common arrhythmia in clinic, atrial fibrillation (AF) causes various comorbidities to patients such as heart failure and stroke. LncRNAs were reported involved in pathogenesis of AF, yet, little is known about AF-associated lncRNAs. The present study aims to explore lncRNAs associated with AF susceptibility based on competing endogenous RNA (ceRNA) network analysis and weighted gene co-expression network analysis (WGCNA). Methods GSE41177 and GSE79768 datasets were obtained from the Gene Expression Omnibus (GEO) database. Competing endogenous RNA (ceRNA) network analysis was performed using GSE41177. Differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs) between AF patients and patients with sinus rhythm (SR) were identified from GSE41177 using R software. Then, the ceRNA network was constructed based on DElncRNAs, the predicted target miRNAs and DEmRNAs. Weighted gene co-expression network analysis (WGCNA) was performed using GSE79768 to validate the AF-related lncRNAs identified from GSE41177. LncRNA modules and crucial lncRNAs relevant to AF and were identified. Results In summary, 18 DElncRNAs and 350 DEmRNAs were found between AF patients and SR patients. A total of 5 lncRNAs, 10 miRNAs, and 21 mRNAs were contained in the final ceRNA network. Taking into consideration both the ceRNA theory and inference scores from the comparative toxicogenomics database (CTD) database, the ceRNA axis FAM201A-miR-33a-3p-RAC3 was identified as mostly relevant to AF susceptibility. FAM201A (Gene significance, GS = − 0.62; Module membership, MM = 0.75) was also proved in the blue module, which was identified most highly relevant with AF by WGCNA. Conclusions These results demonstrated that decreased expression of FAM201A might be associated with susceptibility of AF. Working as the ceRNA to regulate RAC3 might be one function of FAM201A in AF susceptibility, which requires further exploration in future research.

Integrated analysis of the lncRNA-miRNA-mRNA network based on competing endogenous RNA in atrial fibrillation

“…The expression of lncRNA is highly tissue- and cell type-specific, and the mechanisms of lncRNAs acting as ceRNAs in human AF remain unclear. Chen et al constructed an AF-related ceRNA network by identifying lncRNAs from the GSE41177 and GSE79768 datasets, and they reported that lncRNA FAM201A acts as a miRNA sponge of miR-33a-3p to upregulate the expression of the Rac family small GTPase 3 (RAC3) target gene, thereby participating in the regulation of AF susceptibility ( 24 ). In the present study, we found that the target genes of the lncRNA network were mainly involved in the adaptive immune response, inflammatory response, T/B cell receptor signaling pathway, and calcium signaling pathway.…”

Novel Gene Polymorphisms for Stable Warfarin Dose in a Korean Population: Genome-Wide Association Study

“…Aside from its role in cancers, a decrease in FAM201A expression has been linked to osteonecrosis of the femoral head [ 32 ]. Recently, Chen et al revealed that FAM201A was associated with an increased susceptibility to atrial fibrillation through ceRNA network analysis [ 33 ]. This study indicated that the down-regulation of FAM201A could potentially be used as a predictive marker for atrial fibrillation susceptibility.…”

Reviewing Atrial Fibrillation Pathophysiology from a Network Medicine Perspective: The Relevance of Structural Remodeling, Inflammation, and the Immune System

“…For example, FAM201A (the family with sequence similarity 201 member A) is an RNA gene affiliated with the lncRNA class. The decrease in lncRNA FAM201A expression is related to mRNA RAC3 downregulation favoring autophagy, which could lead to a decrease in the L-type calcium channel expression and current, shortening the action potential duration [ 32 ]. Likewise, cardiac apoptosis-related lncRNA competitively binds to miR-539, preventing the miR-539-dependent downregulation of the protein PHB2.…”