miR‑124 inhibits cardiomyocyte apoptosis in myocardial ischaemia‑reperfusion injury by activating mitochondrial calcium uniporter regulator 1

Guo,Linlin; Liu,Chaoying; Jiang,Chunyan; Dong,Yanhan; Htet Htet Aung,Lynn; Ding,Han; Gao,Yanyan

doi:10.3892/mmr.2023.13031

miR‑124 inhibits cardiomyocyte apoptosis in myocardial ischaemia‑reperfusion injury by activating mitochondrial calcium uniporter regulator 1

Authors:
- Linlin Guo
- Chaoying Liu
- Chunyan Jiang
- Yanhan Dong
- Lynn Htet Htet Aung
- Han Ding
- Yanyan Gao
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Affiliations: Department of Cardiovascular Medicine, The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266071, P.R. China, Oncology Department, The People's Hospital of Rizhao, Rizhao, Shandong 276827, P.R. China, Experimental Animal Center, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, P.R. China, Institute for Translational Medicine, Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China
Published online on: June 13, 2023 https://doi.org/10.3892/mmr.2023.13031
Article Number: 144

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Abstract

Mitochondria‑mediated apoptosis is the primary cause of cardiomyocyte death. Therefore, mitochondria are a key target for treating myocardial injury. Mitochondrial calcium uniporter regulator 1 (MCUR1)‑mediated mitochondrial calcium homeostasis markedly promotes cell proliferation and resistance to apoptosis. However, whether MCUR1 is involved in regulation of cardiomyocyte apoptosis during myocardial ischaemia‑reperfusion remains unknown. microRNA‑124 (miR‑124) is upregulated in cardiovascular disease, suggesting a key role for miR‑124 in the cardiovascular system. Whether miR‑124 affects cardiomyocyte apoptosis and myocardial infarction is not well understood. Western blot showed that miR‑124 and MCUR1 were upregulated in cardiomyocyte apoptosis induced by hydrogen peroxide (H₂O₂). Flow cytometry assay of cell apoptosis showed that miR‑124 inhibited cardiomyocyte apoptosis by activating MCUR1 following H2O2 treatment. The dual‑luciferase reporter assay confirmed binding of miR‑124 to MCUR1 3'‑UTR and subsequent activation of MCUR1. FISH assay revealed the entry of miR‑124 into the cell nucleus. Therefore, MCUR1 was identified as a novel target of miR‑124, and it was shown that the miR‑124‑MCUR1 axis modulated cardiomyocyte apoptosis induced by H₂O₂ in vitro. The results indicated induced expression of miR‑124 during acute myocardial infarction and its transport to the nucleus. In the nucleus, miR‑124 transcriptionally activated MCUR1 by binding to its enhancers. These findings reveal a role of miR‑124 as a biomarker for myocardial injury and infarction.

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