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MiR-7a-5p Attenuates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Targeting VDAC1

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Abstract

MicroRNA-7a-5p (miR-7a-5p) is closely related to apoptosis and plays an important role in ischemia/reperfusion (I/R) injury. Whether miR-7a-5p is involved in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis is unknown. Therefore, this study aims to evaluate the role of miR-7a-5p in cardiomyocyte H9C2 cells in response to H/R stimulation. The results of RT-qPCR demonstrated that the expression level of miR-7a-5p was significantly down-regulated in H/R-treated H9C2 cells. MTT assay revealed that the cell viability was notably decreased in H/R group. Flow cytometric analysis found that the ratio of apoptotic cells was increased markedly following H/R. Enforced miR-7a-5p expression increased cell viability and decreased the apoptotic rate. Western blot analysis revealed that the expressions of pro-apoptotic proteins cleaved caspase-3 and Bax were down-regulated, while the expression of anti-apoptotic protein Bcl-2 was up-regulated in H/R-treated H9C2 cells transfected with miR-7a-5p mimic. On the contrary, miR-7a-5p downexpressing promoted apoptosis in H/R-treated H9C2 cells. Furthermore, the bioinformatics prediction manifested voltage-dependent anion channel 1 (VDAC1) was a potential target for miR-7a-5p, and dual-luciferase reporter assay confirmed that miR-7a-5p targeted VDAC1 3′ untranslated regions, which leads to the repressed expressions of VDAC1 mRNA and protein. Knockdown of VDAC1 potentiated the protective effects of miR-7a-5p against H/R-induced cell injury. In conclusion, our results demonstrated that miR-7a-5p is involved in H/R-induced cardiomyocyte apoptosis through targeting VDAC1. MiR-7a-5p/VDAC1 axis might be utilized as hopeful biomarkers to reveal the potential mechanism of myocardial I/R injury.

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Acknowledgements

Thanks for all the contributors and participants.

Funding

This research was funded by the Grants from the Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi Universities (2020KY03014).

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Authors and Affiliations

  1. Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China

    Hailin Lu & Feifei Xuan

  2. Department of Vascular Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China

    Jiangfeng Zhang

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  1. Hailin Lu
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Correspondence to Feifei Xuan.

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Lu, H., Zhang, J. & Xuan, F. MiR-7a-5p Attenuates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Targeting VDAC1. Cardiovasc Toxicol 22, 108–117 (2022). https://doi.org/10.1007/s12012-021-09705-7

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