Genome-wide profiling reveals atrial fibrillation-related circular RNAs in atrial appendages

Atrial fibrillation (AF) is an abnormal heart rhythm characterized by rapid and irregular beating of the atria. The non-coding RNAs (ncRNAs) have attracted much attention of AF researchers, as they play a critical role in the transcriptional and post-transcriptional regulation, which could greatly benefit the interpretation of the pathogenesis of AF. However, circRNAs, as a special member of the ncRNAs, and their role in the pathogenesis of AF is less understood. In the present study, we detected a total of 14,215 circRNAs in AF patients and healthy controls. Differential expression analysis of these circRNAs revealed 20 upregulated and 3 downregulated circRNAs, which were differentially expressed in both left and right atrial appendages. The association analysis of the AF-related circRNAs and their parental genes revealed that hsa_circ_0003965 had significantly negative correlation with its parental gene TMEM245 (PCC = -0.51), suggesting that the dysregulation of hsa_circ_0003965 was not regulated by the transcription of its parental gene, but could be associated with glucagon signaling pathway. The competing endogenous RNA (ceRNA) network analysis revealed two upregulated genes, IFNG and GDF7, and one downregulated gene, BMP7, all of which were involved in TGF-beta signaling pathway, which further suggested that these circRNAs, namely hsa_circ_0000075 and hsa_circ_0082096, participated in the AF pathogenesis via TGF-beta signaling pathway. Consistently, TGF-beta signaling pathway was a well-recognized player for its association with atrial fibrosis in AF. In summary, we aimed to discover and provide key circRNAs involved in AF for AF-related researchers, which had the potential to greatly improve our understanding of the underlying mechanism behind circRNAs and AF.