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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Cardiac Rhythmology
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1400643

Identification of miR-1 and miR-499 in Chronic Atrial Fibrillation by Bioinformatics Analysis and Experimental Validation

Provisionally accepted
Xinpei Chen Xinpei Chen 1,2,3Yu Zhang Yu Zhang 4Meng He Meng He 5Guiying Chen Guiying Chen 5Yongjiang Ma Yongjiang Ma 6Jian Li Jian Li 2Saizhe Liu Saizhe Liu 2Zhuo Liang Zhuo Liang 4Yinuo Xie Yinuo Xie 2Ying Liu Ying Liu 7Hongyang Guo Hongyang Guo 2Yutang Wang Yutang Wang 2Zhaoliang Shan Zhaoliang Shan 8*
  • 1 Ludwig Maximilian University of Munich, Munich, Bavaria, Germany
  • 2 First Affiliated Hospital of Chinese PLA General Hospital, Beijing, Beijing Municipality, China
  • 3 Yunnan Fuwai Cardiovascular Hospital, Kunming, Yunnan Province, China
  • 4 Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, Beijing, China
  • 5 Tianjin Chest Hospital, Tianjin, Tianjin Municipality, China
  • 6 Sixth Medical Center of PLA General Hospital, Beijing, Beijing Municipality, China
  • 7 General Hospital of Beijing Jingmei Group, Beijing, China
  • 8 Department of Cardiology, Chinese PLA General Hospital, Beijing, China

The final, formatted version of the article will be published soon.

    Background: Atrial fibrillation (AF) is one of the most prevalent arrhythmias and is characterized by a high risk of heart failure and embolic stroke, yet its underlying mechanism is unclear. The primary goal of this study was to establish a miRNA-mRNA network and identify the miRNAs associated with chronic AF by bioinformatics and experimental validation.The GSE79768 dataset was collected from the Gene Expression Omnibus(GEO) database to extract data from patients with or without persistent AF. Differentially expressed genes (DEGs) were identified in left atrial appendages (LAAs). The STRING platform was utilized for protein-protein interaction (PPI) network analysis. The target miRNAs for the top 20 hub genes were predicted by using the miRTarBase Web tool. The miRNA-mRNA network was established and visualized using Cytoscape software. The key miRNAs selected for verification in the animal experiment were confirmed by miRwalk Web tool. We used a classic animal model of rapid ventricular pacing for chronic AF. Two groups of animals were included in the experiment, namely, the ventricular pacing group (VP group), where ventricular pacing was maintained at 240-280 bpm for 2 weeks, and the control group was the sham-operated group (SO group). Finally, we performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to validate the expression of miR-1 and miR-499 in LAA tissues of the VP group and the SO group. Left atrial fibrosis and apoptosis were evaluated by Masson staining and caspase-3 activity assays, respectively.The networks showed 48 miRNAs in LAA tissues. MiR-1 and miR-499 were validated using an animal model of chronic AF. The expression level of miR-1 was increased, and miR-499 was decreased in VP group tissues compared to SO group tissues in LAAs (P < 0.05), which were correlated with left atrial fibrosis and apoptosis in AF.This study provides a better understanding of the alterations in miRNA-1 and miR-499 in chronic AF from the perspective of the miRNA-mRNA network and corroborates findings through experimental validation. These findings may offer novel potential therapeutic targets for AF in the future.

    Keywords: Atrial Fibrillation, Differentially expressed genes, bioinformatics, microRNAs(miRNAs), MiRNA-mRNA regulatory network

    Received: 13 Mar 2024; Accepted: 31 Jul 2024.

    Copyright: © 2024 Chen, Zhang, He, Chen, Ma, Li, Liu, Liang, Xie, Liu, Guo, Wang and Shan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zhaoliang Shan, Department of Cardiology, Chinese PLA General Hospital, Beijing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.