MiR-31a-5p protects myocardial cells against apoptosis by targeting Tp53

  • Authors:
    • Meng‑Jie Yan
    • Zhi‑Sen Tian
    • Zhi‑Hui Zhao
    • Ping Yang
  • View Affiliations

  • Published online on: December 27, 2017     https://doi.org/10.3892/mmr.2017.8357
  • Pages: 3898-3904
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Abstract

The pathogenesis and progression of heart failure (HF) involves multiple mechanisms, including the increased activity of the renin-angiotensin-aldosterone system, apoptosis and differential expression of microRNAs (miRNAs/miRs). Our previous study revealed an increase in miR‑31a‑5p levels in the failing hearts of a rat HF model. In the present study, whether and how miR‑31a‑5p mediates angiotensin II (AngII)‑induced apoptosis in the cardiac H9C2 cell line, was investigated using molecular biological approaches, including reverse transcription followed by quantitative polymerase chain reaction, western blotting, RNA arrays, and mutagenesis. It was demonstrated that AngII stimulation increased apoptosis and decreased miR‑31a‑5p expression, which coincided with increased tumor protein p53 (Tp53) levels. Overexpression of miR‑31a‑5p significantly suppressed the AngII‑induced apoptotic rate and caspase‑3 activity, while suppression of miR‑31a‑5p did the opposite. A total of 16 proapoptotic genes that were downregulated and 4 antiapoptotic genes that were upregulated in the miR‑31a‑5p‑overexpressed cells were identified. It was also revealed that Tp53 mRNA contained the seed sequence in its 3'‑untranslated region for miR‑31a‑5p binding. The luciferase reporter analysis showed that miR‑31a‑5p repressed the luciferase activity of the wild‑type seed sequence, but not the mutated seed sequence fused to a reporter construct. Thus, it was demonstrated that miR‑31a‑5p mediated AngII‑triggered apoptosis in myocardial cells at least partially through targeting Tp53. These findings advance the understanding of the functional interaction between miRNAs and Tp53 in the setting of cardiac diseases. Further work is required to explore whether miR‑31a‑5p can serve as a therapeutic target for HF treatment in vivo.
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March-2018
Volume 17 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yan MJ, Tian ZS, Zhao ZH and Yang P: MiR-31a-5p protects myocardial cells against apoptosis by targeting Tp53. Mol Med Rep 17: 3898-3904, 2018
APA
Yan, M., Tian, Z., Zhao, Z., & Yang, P. (2018). MiR-31a-5p protects myocardial cells against apoptosis by targeting Tp53. Molecular Medicine Reports, 17, 3898-3904. https://doi.org/10.3892/mmr.2017.8357
MLA
Yan, M., Tian, Z., Zhao, Z., Yang, P."MiR-31a-5p protects myocardial cells against apoptosis by targeting Tp53". Molecular Medicine Reports 17.3 (2018): 3898-3904.
Chicago
Yan, M., Tian, Z., Zhao, Z., Yang, P."MiR-31a-5p protects myocardial cells against apoptosis by targeting Tp53". Molecular Medicine Reports 17, no. 3 (2018): 3898-3904. https://doi.org/10.3892/mmr.2017.8357