Identification of Long Non-Coding RNA and Circular RNA Expression Profiles in Atrial Fibrillation

Abstract

Long non-coding RNA (lncRNA) and circular RNA (circRNA) have both been found to play important roles in cardiovascular diseases, including myocardial infarction, heart failure, and atherosclerosis. However, the role of lncRNA and circRNA in atrial fibrillation (AF) has rarely been investigated. This study aimed to identify lncRNA and circRNA expression profiles in AF patients. Atrial tissues from seven patients with AF and seven matched controls were collected. The lncRNA and circRNA expression profiles of atrial tissues were identified using Hiseq/Proton RNA sequencing. Validation was performed by reverse transcription quantitative real-time PCR (qRT-PCR) on 35 pairs of AF patients and controls. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A competing endogenous RNA (ceRNA) network was constructed. A total of 557 lncRNAs and 280 circRNAs were significantly differentially expressed with fold change >1.5 (p<0.05). An lncRNA Voltage Dependent Anion Channel 2 Pseudogene 2 (VDAC2P2) and two circRNAs chr13_41887361_41865736_-21625 and chr13_100368574_100301460_-67114 were validated, using qRT-PCR, to have significantly different expression levels. GO and KEGG pathway analysis showed that some pathways such as ribosome and chromatin modification, Rap1 signalling and cardiac muscle contraction were involved in the pathogenesis of AF. Competing endogenous RNAs were predicted based on constructional network analysis. The LncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed by co-expressing lncRNA/circRNA and mRNAs, which were competitively combined with miRNAs. This study characterised lncRNA and circRNA expression and their interaction with mRNA and miRNA in AF.