Abstract
Long noncoding RNAs (lncRNAs) have been suggested to play indispensable roles in multiple heart diseases. However, the correlations between lncRNAs and atrial fibrillation (AF) are unclear. In this study, we performed comprehensive lncRNA profiling via high-throughput RNA sequencing analysis using non-AF and AF rabbit models. Based on a series of filtering pipelines and bioinformatics analyses, TCONS-00106987 was selected for further research. TCONS-00106987 levels were increased in the atria during AF. Moreover, the atrial effective refractory period was shortened and the AF inducibility was increased in vivo in response to lentiviral-mediated up-regulation of TCONS-00106987. TCONS-00106987 repression resulted in the opposite effects. Further studies indicated that TCONS-00106987 expression was positively correlated with the expression of the protein-coding gene KCNJ2. Luciferase reporter assays and whole-cell patch-clamp recording confirmed that TCONS-00106987 promoted electrical remodelling via endogenous competition with microRNA-26 (miR-26) to induce transcription of its target gene KCNJ2, thereby increasing inward-rectifier K+ current (IK1 ). In conclusion, our study reveals a pathogenic lncRNA-miRNA regulatory network specific to atrial electrical remodelling that offers potential therapeutic targets for AF.