lncRNA KCNQ1OT1 may function as a competitive endogenous RNA in atrial fibrillation by sponging miR-223-3p

Atrial fibrillation (AF) is one of the most common forms of cardiac arrhythmia. Novel evidence has indicated that a competing endogenous RNA (ceRNA) mechanism may occur in AF. The present study aimed to identify differentially expressed microRNAs (miRNAs/miRs) in AF and predict their targeting long non-coding RNAs (lncRNAs) to identify a potential ceRNA network involved in AF using bioinformatics analysis. The GSE68475 microarray dataset was downloaded from the Gene Expression Omnibus database and differentially expressed miRNAs in AF were obtained. In addition, right atrial appendage (RAA) tissues from patients with AF were collected to determine the expression levels of the miRNAs identified following bioinformatics analysis using reverse transcription-quantitative PCR (n=8 per group). Subsequently, Gene Ontology (GO) functional term and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analyses of the target genes of differentially expressed miRNAs of interest were performed. The potential upstream lncRNAs targeting the identified miRNAs were predicted using bioinformatics analysis. A dual luciferase reporter assay was used to verify the existence of a targeted relationship between the differentially expressed miRNA and lncRNA of interest. The results identified 43 differentially expressed miRNAs, including 23 upregulated miRNAs. The trends in the expression levels of miR-223-3p were inconsistent between the microarray data and those recorded in the RAA tissues from patients with persistent AF. Therefore, miR-223-3p was selected as the miRNA of interest for further investigations. The target gene of miR-233-3p was found to be enriched in 57 GO terms and 21 KEGG signaling pathways. According to the bioinformatics prediction, 69 lncRNAs targeting miR-223-3p were identified, including the lncRNA growth arrest-specific transcript 5, lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and lncRNA MYC-induced long non-coding RNA. The results from dual luciferase assay confirmed that miR-223-3p was a direct target of KCNQ1OT1. A ceRNA regulatory relationship may exist between KCNQ1OT1 and miR-223-3p in AF, providing therefore a novel potential research target for further studies.