MicroRNA‑138‑5p drives the progression of heart failure via inhibiting sirtuin 1 signaling

Sun,Shuai; Wang,Chun; Weng,Jianxin

doi:10.3892/mmr.2021.11915

MicroRNA‑138‑5p drives the progression of heart failure via inhibiting sirtuin 1 signaling

Authors:
- Shuai Sun
- Chun Wang
- Jianxin Weng
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Affiliations: Department of Cardiology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518000, P.R. China
Published online on: February 11, 2021 https://doi.org/10.3892/mmr.2021.11915
Article Number: 276
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the regulatory effects of microRNA‑138‑5p (miR‑138‑5p) and sirtuin 1 (SIRT1) on the progression of heart failure (HF). The binding association between miR‑138‑5p and SIRT1 was assessed by the dual‑luciferase reporter assay. By conducting reverse transcription‑quantitative polymerase chain reaction and Western blotting, relative levels of SIRT1 and p53 regulated by miR‑138‑5p were detected. In vitro HF models were generated by hydrogen peroxide (H₂O₂) induction in AC‑16 and human cardiomyocyte (HCM) cells, followed by detection of the regulatory effects of SIRT1 on cell apoptosis and p53 expression. MiR‑138‑5p was negatively correlated with the SIRT1 level in cardiomyocytes. By recognizing and specifically targeting SIRT1 3'‑untranslated region (3'‑UTR), miR‑138‑5p decreased the translational level of SIRT1 and inhibited its enzyme activity, thereby decreasing the deacetylation level of p53. Through downregulating SIRT1 and activating p53 signaling, miR‑138‑5p induced apoptosis in H₂O₂‑induced AC‑16 and HCM cells. By contrast, knockdown of miR‑138‑5p in the in vitro HF models significantly protected the cardiomyocytes. SIRT1 contributed toward alleviate HF by inhibiting cardiomyocyte apoptosis via enhancing the deacetylation level of p53. MiR‑138‑5p decreases the enzyme activity of SIRT1 by specifically targeting its 3'‑UTR and activates p53 signaling, followed by triggering cardiomyocyte apoptosis during the process of HF. It is considered that miR‑138‑5p and SIRT1 may be potential diagnostic biomarkers and therapeutic targets for HF.

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