Integrative Analysis Reveals Key Circular RNA in Atrial Fibrillation

Abstract

Circular RNAs (circRNAs) are an emerging class of RNA species that may play a critical regulatory role in gene expression control, which can serve as diagnostic biomarkers for many diseases due to their abundant, stable, and cell- or tissue-specific expression. However, the association between circRNAs and atrial fibrillation (AF) is still not clear. In this study, we used RNA sequencing data to identify and quantify the circRNAs. Differential expression analysis of the circRNAs identified 250 up- and 126 down-regulated circRNAs in AF subjects compared with healthy donors, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the parental genes of the dysregulated circRNAs indicated that the up-regulated parental genes may participate in the process of DNA damage under oxidative stress. Furthermore, to annotate the dysregulated circRNAs, we constructed and merged the competing endogenous RNA (ceRNA) network and protein-protein interaction (PPI) network, respectively. In the merged network, 130 of 246 dysregulated circRNAs were successfully characterized by more than one pathway. Notably, the five circRNAs, including chr9:15474007-15490122, chr16:75445723-75448593, hsa_circ_0007256, chr12:56563313-56563992, and hsa_circ_0003533, showed the highest significance by the enrichment analysis, and four of them were enriched in cytokine-cytokine receptor interaction. These dysregulated circRNAs may mainly participate in biological processes of inflammatory response. In conclusion, the present study identified a set of dysregulated circRNAs, and characterized their potential functions, which may be associated with inflammatory responses in AF. To our knowledge, this is the first study to uncover the association between circRNAs and AF, which not only improves our understanding of the roles of circRNAs in AF, but also provides candidates of potentially functional circRNAs for AF researchers.

Differential Expression and Bioinformatics Analysis of CircRNA in PDGF-BB-Induced Vascular Smooth Muscle Cells

“…phenotypes, we think that the screening algorithm we used may be too strict, and the results may lose a large number of true positive results. Therefore, we changed the screening criteria, using the criteria of log2 (fold change) >1 or log2 (fold change) <−1 and P value <0.05 as previous studies (Dang et al, 2017;Xu et al, 2018;Hu et al, 2019) to screen out 112 different expression circRNAs between PS and NC, and then randomly selected 10 circRNAs for verification experiment. On the basis of verification, we calculated the false positive rate (FPR) to generate the Q value.…”

Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis

“…Though atrial fibrillation (AF) is the most common type of arrhythmia in the general population, ventricular arrhythmia (VA) is the major mechanism of SCD in IHD [ 57 , 98 ]. Some studies revealed that circRNAs participate in AF by the identification and characterization of circRNA expression profiles, and provide novel biomarkers and potential therapeutic targets for AF [ 99 ]. However, the expression and function of circRNAs in VAs were not experimentally confirmed.…”

CircRNAs open a new era in the study of cardiovascular disease (Review)

“…Another study revealed that the expression of circANRIL subtypes were inversely correlated with the risk and the severity of AS ( 85 ). Furthermore, a recent study documented for the first time the association between the expression of circRNAs and atrial fibrillation ( 86 ). Therefore, a total of five circRNAs were identified with notable biological significance, including chr9:15474007-15490122, chr16:75445723-75448593, hsa_circ_0007256, chr12:56563313-56563992 and hsa_ circ_0003533.…”