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

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.

Genetics and Epigenetics of Atrial Fibrillation

“…Our current understanding of the expression and functional role of long noncoding RNAs (lncRNAs) in human AF is still incipient. Several transcriptomics analyses have been performed, identifying a large array of differentially expressed lncRNAs [ 177 , 178 , 179 , 180 , 181 , 182 ] in AF. Some of these studies were performed in lone AF patients [ 179 , 180 , 181 ], whereas in others valvular heart disease [ 177 ] or rheumatic valve disease [ 178 , 180 , 182 ] was also concurring.…”

“…Several transcriptomics analyses have been performed, identifying a large array of differentially expressed lncRNAs [ 177 , 178 , 179 , 180 , 181 , 182 ] in AF. Some of these studies were performed in lone AF patients [ 179 , 180 , 181 ], whereas in others valvular heart disease [ 177 ] or rheumatic valve disease [ 178 , 180 , 182 ] was also concurring. In most cases, either right or left atrial appendages were analysed [ 175 , 176 , 177 , 178 , 179 , 180 ], but in some cases right and left atrial samples were pooled together [ 179 , 180 , 181 ], while in other blood samples [ 180 , 183 ] or epicardial adipose tissue [ 184 , 185 ] were analysed.…”

Long Non-Coding RNAs in Atrial Fibrillation: Pluripotent Stem Cell-Derived Cardiomyocytes as a Model System

“…Indeed, previous findings have shown that GATA1 and TAF1 have known roles in AF pathology [ 138 , 139 ]. Ke et al [ 123 ] also performed a differential expression analysis of lncRNAs in the left and right atrium of AF patients and identified two AF-linked lncRNAs (RP11-99E15.2 and RP3-523K23.2) that regulate heat shock factor 2 (HSF2), which is an important player in hypertension-induced HF. Furthermore, Cheng et al [ 124 ] examined lncRNA expression profiles in the left atrial appendage and left atrial tissue surrounding the pulmonary veins, where AF is believed to be initiated, and identified 94 differentially expressed lncRNAs.…”

“…Ke et al [ 123 ] analyzed RNAseq data in left and right atrial appendages from patients with or without AF and identified key RNAs linked with AF. They predicted lncRNAs that potentially regulate adjacent protein-coding genes and found that lncRNA NPPA-AS1, RP11-99E15.2, and RP3-523K23.2 could interact with NPPA, ITGB3, and HSF2, respectively, and may be involved in the pathogenesis of AF.…”

“…NPPA-AS1 has been shown to play a role in AF via modulation of atrial contractile genes [ 123 ]. Celik et al [ 164 ] studied the molecular mechanism of this lncRNA in iPSC-derived cardiomyocytes (iPSC-CMs), which contained a mixture of atrial, ventricular, and nodal CMs.…”