ISSN 2149-2263 | E-ISSN 2149-2271
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Possible key microRNAs and corresponding molecular mechanisms for atrial fibrillation [Anatol J Cardiol]
Anatol J Cardiol. 2020; 23(6): 324-333 | DOI: 10.14744/AnatolJCardiol.2020.39483

Possible key microRNAs and corresponding molecular mechanisms for atrial fibrillation

Huili Zhang1, Guangming Yang2, Ning Zhong3, Jun Shan4, Xiaona Li1, Yanhai Wu3, Yazhou Xu5, Ye Yuan5
1Department of Pharmacy, The Second People’s Hospital of Xinxiang; Henan-China
2Department of Emergency, The Second People’s Hospital of Xinxiang; Henan-China
3Department of Cardiovasology, The Second People’s Hospital of Xinxiang; Henan-China
4Department of General Medicine, The Second People’s Hospital of Xinxiang; Henan-China
5Henan Zhongping Genetic Technology Co., Ltd., Zhengzhou; Henan-China

Objective: We aimed to find crucial microRNAs (miRNAs) associated with the development of atrial fibrillation (AF), and then try to elucidate the possible molecular mechanisms of miRNAs in AF.
Methods: The miRNA microarray, GSE68475, which included 10 right atrial appendage samples from patients with persistent AF and 11 samples from patients with normal sinus rhythm, was used for the analysis. After data preprocessing, differentially expressed miRNAs were screened using limma. Target genes of miRNAs were predicted using miRWalk2.0. We then conducted functional enrichment analyses for miRNA and target genes. Protein-protein interaction (PPI) network and module analyses for target genes were performed. Finally, transcription factors (TFs)-target genes regulatory network was predicted and constructed.
Results: Seven genes, including CAMK2D, IGF2R, PPP2R2A, PAX6, POU3F2, YWHAE, and AP2A2, were targeted by TFs. Among these seven genes, CAMK2D (targeted by miR-31-5p), IGF2R (targeted by miR-204-5p), PAX6 (targeted by miR-223-3p), POU3F2 (targeted by miR-204-5p), YWHAE (targeted by miR-31-5p), and AP2A2 (targeted by miR-204-5p) belonged to the top 10 degree genes in the PPI network. Notably, MiR-204-5p, miR-31-5p, and miR-223-3p had more target genes. Besides, CAMK2D was enriched in some pathways, such as adrenergic signaling in cardiomyocytes pathway and cAMP signaling pathway. YWHAE was enriched in the Hippo signaling pathway.
Conclusion: miR-31-5p played a crucial role in cardiomyocytes by targeting CAMK2D and YWHAE via cAMP and Hippo signaling pathways. miR-204 was involved in the progression of AF by regulating its target genes IGF2R, POU3F2, and AP2A2. On the other hand, miR-223-3p functioned in AF by targeting PAX6, which was associated with the regulation of apoptosis in AF. This study would provide a theoretical basis and potential therapeutic targets for the treatment of AF. (Anatol J Cardiol 2020; 23: 324-33)

Keywords: atrial fibrillation, microRNAs, differentially expressed genes, pathways

Huili Zhang, Guangming Yang, Ning Zhong, Jun Shan, Xiaona Li, Yanhai Wu, Yazhou Xu, Ye Yuan. Possible key microRNAs and corresponding molecular mechanisms for atrial fibrillation. Anatol J Cardiol. 2020; 23(6): 324-333

Corresponding Author: Huili Zhang, China
Manuscript Language: English


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