RNA sequencing profiling reveals key mRNAs and long noncoding RNAs in atrial fibrillation

J Cell Biochem. 2020 Aug;121(8-9):3752-3763. doi: 10.1002/jcb.29504. Epub 2019 Nov 3.

Abstract

Long noncoding RNAs (lncRNAs) are an emerging class of RNA species that could participate in some critical pathways and disease pathogenesis. However, the underlying molecular mechanism of lncRNAs in atrial fibrillation (AF) is still not fully understood. In the present study, we analyzed RNA-seq data of paired left and right atrial appendages from five patients with AF and other five patients without AF. Based on the gene expression profiles of 20 samples, we found that a majority of genes were aberrantly expressed in both left and right atrial appendages of patients with AF. Similarly, the dysregulated pathways in the left and right atrial appendages of patients with AF also bore a close resemblance. Moreover, we predicted regulatory lncRNAs that regulated the expression of adjacent protein-coding genes (PCGs) or interacted with proteins. We identified that NPPA and its antisense RNA NPPA-AS1 may participate in the pathogenesis of AF by regulating the muscle contraction. We also identified that RP11 - 99E15.2 and RP3 - 523K23.2 could interact with proteins ITGB3 and HSF2, respectively. RP11 - 99E15.2 and RP3 - 523K23.2 may participate in the pathogenesis of AF via regulating the extracellular matrix binding and the transcription of HSF2 target genes, respectively. The close association of the lncRNA-interacting proteins with AF further demonstrated that these two lncRNAs were also associated with AF. In conclusion, we have identified key regulatory lncRNAs implicated in AF, which not only improves our understanding of the lncRNA-related molecular mechanism underlying AF but also provides computationally predicted regulatory lncRNAs for AF researchers.

Keywords: Long noncoding RNAs (LncRNAs); NPPA-AS1; atrial fibrillation (AF); lncRNA-interacting proteins; regulatory lncRNAs.