Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a high incidence of stroke. Many circular RNAs (circRNAs) have been demonstrated they are elated to various heart diseases and may play important roles in diagnostics or many pathophysiological processes. Nevertheless, there is Few studies on circRNAs functions in persistent AF. To identify AF-related circRNAs and construct the integrative regulatory network of circular RNAs, miRNAs, and mRNAs, we collected human right atrial appendage tissues from 5 patients suffering persistent AF (AF group) and 5 patients with normal sinus rhythm (NSR group) and characterized the global changes in circRNA expression with high-throughput sequencing technology. The differential expression of circRNAs and the interactions between circRNAs and microRNAs were analyzed. The microRNA expression file GSE68475 dataset was downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed microRNAs. The target genes of overlapped miRNAs were predicted by using DIANA-TarBase v8. We constructed the circRNA- miRNA-mRNA network using Cytoscape (version 3.4.0) and the network topology was analyzed by utilizing CentiScaPe app. Results showed that all of 600 differentially expressed circRNAs related to AF were screened, including 340 up-regulated and 260 down-regulated circRNAs. An integrative regulatory network was constructed, which included 30 circRNAs, 9 miRNAs and 130 target mRNAs of these miRNAs. It was concluded that that 30 circRNAs, including 8 upregulated circRNAs and 22 downregulated circRNAs, were predicted to highly possibly function as sponges of 9 miRNAs to regulate gene expression by using bioinformatics analysis. Moreover, the interactions of hsa-miR-339-5p with its related circRNAs and target mRNAs constructed the hub regulatory network in persistent AF by utilizing topology analysis. Our proposed regulatory network of circRNAs-miRNAs-mRNAs may provide new insight into the potential mechanism underlying persistent AF. Additionally, these important molecular may become novel biomarkers providing a new strategy in diagnosis and therapy of AF.

Highlights

  • Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia which influences approximately 1.5% of the total population [1], and more than 50% of paroxysmal AF will progress to persistent AF within 10 years [2]

  • Over the past few decades, many researches have demonstrated that large numbers of mRNAs were associated with the development and progression of atrial fibrillation (AF), the molecular mechanism underlying AF remains unclear owing to the fact that more focus has been put on mRNAs or miRNAs [26, 27]

  • Identification new circRNAs relating to atrial fibrillation could provide novel insight into the potential mechanisms of AF

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Summary

Introduction

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia which influences approximately 1.5% of the total population [1], and more than 50% of paroxysmal AF will progress to persistent AF within 10 years [2]. AF, sometimes referred to in medicine as AFib, does not have a specific electrical stimulation in the heart. It occurs when there is no electrical stimulation wave in the atria in a specific direction, ie the atrial muscle cells are irregularly stimulated and as a result contract. Cardiac arrhythmia means that the heart rhythm is abnormal. The heart rhythm starts at the sinus node and spreads to the ventricles after transfer to the atrioventricular node. As a result of this way of conducting electrical stimulation, the atria first contract and the ventricles contract at short intervals, and the atrial muscles relax and the ventricles relax [8, 9]

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