Open Access

miR‑141 impairs mitochondrial function in cardiomyocytes subjected to hypoxia/reoxygenation by targeting Sirt1 and MFN2

  • Authors:
    • Hao Zhang
    • Yaqiao Wang
    • Kehan Wu
    • Runmin Liu
    • Hao Wang
    • Yongwei Yao
    • Peter Kvietys
    • Tao Rui
  • View Affiliations

  • Published online on: November 14, 2022     https://doi.org/10.3892/etm.2022.11699
  • Article Number: 763
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitochondrial oxidative stress and dysfunction are major pathogenic features of cardiac injury induced by ischemia/reperfusion (I/R). MicroRNA‑141 (miR‑141) has been implicated in the mitochondrial dysfunction in cell‑based models of oxidant stress. Thus, the main aim of the present study was to systematically assess the role of miR‑141 in cardiomyocyte injury induced by simulated I/R. The challenge of HL‑1 cardiomyocytes with hypoxia/reoxygenation (H/R) decreased cell viability, which was also associated with an increase in miR‑141 expression. The H/R‑induced cell injury was mitigated by a miR‑141 inhibitor and exacerbated by a miR‑141 mimic. Furthermore, H/R induced mitochondrial superoxide production, dysfunction (decreased oxygen utilization and membrane depolarization), as well as ultrastructural damage. These mitochondrial effects were mitigated by a miR‑141 inhibitor and intensified by a miR‑141 mimic. Luciferase reporter assay, reverse transcription‑quantitative PCR, and western blot analyses identified sirtuin‑1 (Sirt1) and mitofusin‑2 (MFN2) as targets of miR‑141. The silencing of Sirt1 reduced the MFN2 cardiomyocyte levels and reversed the alleviating effects of miR‑141 inhibitor on mitochondrial function during H/R. Collectively, these findings suggest that miR‑141 functions as a causative agent in cardiomyocyte injury induced by I/R, primarily by interfering with two mitochondrial regulatory proteins, Sirt1 and MFN2.

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December-2022
Volume 24 Issue 6

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Spandidos Publications style
Zhang H, Wang Y, Wu K, Liu R, Wang H, Yao Y, Kvietys P and Rui T: miR‑141 impairs mitochondrial function in cardiomyocytes subjected to hypoxia/reoxygenation by targeting Sirt1 and MFN2. Exp Ther Med 24: 763, 2022
APA
Zhang, H., Wang, Y., Wu, K., Liu, R., Wang, H., Yao, Y. ... Rui, T. (2022). miR‑141 impairs mitochondrial function in cardiomyocytes subjected to hypoxia/reoxygenation by targeting Sirt1 and MFN2. Experimental and Therapeutic Medicine, 24, 763. https://doi.org/10.3892/etm.2022.11699
MLA
Zhang, H., Wang, Y., Wu, K., Liu, R., Wang, H., Yao, Y., Kvietys, P., Rui, T."miR‑141 impairs mitochondrial function in cardiomyocytes subjected to hypoxia/reoxygenation by targeting Sirt1 and MFN2". Experimental and Therapeutic Medicine 24.6 (2022): 763.
Chicago
Zhang, H., Wang, Y., Wu, K., Liu, R., Wang, H., Yao, Y., Kvietys, P., Rui, T."miR‑141 impairs mitochondrial function in cardiomyocytes subjected to hypoxia/reoxygenation by targeting Sirt1 and MFN2". Experimental and Therapeutic Medicine 24, no. 6 (2022): 763. https://doi.org/10.3892/etm.2022.11699