Wei Feiyu, Zhang Xi, Kuang Xiaohui, Gao Xiaolong, Wang Jing, Fan Jie
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.
Department of Cardiology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
Front Cardiovasc Med. 2022 Jun 30;9:883205. doi: 10.3389/fcvm.2022.883205. eCollection 2022.
Atrial fibrillation (AF) is one of the most prevalent arrhythmias, characterized by a high risk of heart failure and embolic stroke. Competing endogenous RNA network has been reported to play an important role in cardiovascular diseases. The main objective of the present study was to construct a circRNA-miRNA-mRNA-mediated network and explore the potential function in AF.
The microarray data of circRNA, miRNA, and mRNA in AF were downloaded from the Gene Expression Omnibus database. The RobustRankAggreg method was used to screen the different expression circRNAs(DECs). Then the circRNA-miRNA-mRNA-mediated network was constructed by using the CircInteractome database and the miRWalk online tool. A quantitative real-time polymerase chain reaction was used to detect the circRNA expression level in plasma. The left atrial fibrosis was evaluated with the left atrial low voltage area (LVA) by using left atrial voltage matrix mapping.
Three DECs (hsa_circRNA_102461, hsa_circRNA_103693, and hsa_circRNA_059880) and 4 miRNAs were screened. Then a circRNA-miRNA-mRNA-mediated network was constructed, which included 2 circRNAs, 4 miRNAs, and 83 genes. Furthermore, the plasma's hsa_circ_0070391 expression level was confirmed to be upregulated and positively correlated with left atrial fibrosis in AF ( = 0.88, < 0.001), whereas hsa_circ_0003935 was downregulated. Moreover, the ROC curve analysis revealed hsa_circ_0070391 and hsa_circ_0003935 could differentiate AF from the healthy controls with an AUC of 0.95 (95% sensitivity and 90% specificity) and 0.86 (70% sensitivity and 75% specificity), respectively. Finally, the free of atrial tachyarrhythmia rate was dramatically lower in the hsa_circ_0070391 high expression group than in the low expression group post catheter ablation (70.0 vs. 90.0%, = 0.04).
This study provides a novel insight to further understand the AF pathogenesis from the perspective of the circRNA-miRNA-mRNA network, suggesting that plasma circRNAs could serve as a novel atrial fibrosis and prognosis biomarker for AF.
心房颤动（AF）是最常见的心律失常之一，其特征是心力衰竭和栓塞性中风风险高。据报道，竞争性内源性RNA网络在心血管疾病中起重要作用。本研究的主要目的是构建一个circRNA-miRNA-mRNA介导的网络，并探索其在AF中的潜在功能。
从基因表达综合数据库下载AF中circRNA、miRNA和mRNA的微阵列数据。使用RobustRankAggreg方法筛选差异表达的circRNA（DECs）。然后利用CircInteractome数据库和miRWalk在线工具构建circRNA-miRNA-mRNA介导的网络。采用定量实时聚合酶链反应检测血浆中circRNA的表达水平。使用左心房电压矩阵映射通过左心房低电压区（LVA）评估左心房纤维化。
筛选出3个DECs（hsa_circRNA_102461、hsa_circRNA_103693和hsa_circRNA_059880）和4个miRNA。然后构建了一个circRNA-miRNA-mRNA介导的网络，其中包括2个circRNA、4个miRNA和83个基因。此外，证实AF患者血浆中hsa_circ_0070391表达水平上调，且与左心房纤维化呈正相关（r = 0.88，P < 0.001），而hsa_circ_0003935表达下调。此外，ROC曲线分析显示，hsa_circ_0070391和hsa_circ_0003935能够区分AF与健康对照，AUC分别为0.95（敏感性95%，特异性90%）和0.86（敏感性70%，特异性75%）。最后，导管消融术后hsa_circ_0070391高表达组的房性快速心律失常-free率显著低于低表达组（70.0%对90.0%，P = 0.04）。
本研究为从circRNA-miRNA-mRNA网络角度进一步理解AF发病机制提供了新的见解，表明血浆circRNAs可作为AF新的心房纤维化和预后生物标志物。
