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MicroRNA-9 facilitates hypoxia-induced injury and apoptosis in H9c2 cells via targeting CDK8

Abstract

Hypoxia plays an important role in many heart diseases. MicroRNA-9 (miR-9) has been reported to be involved in hypoxia-induced cell proliferation, injury and apoptosis in cardiomyocytes. However, the underlying mechanism still remains poorly understood. The expression levels of miR-9 and cyclin-dependent kinase 8 (CDK8) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relative protein expression was measured by Western blot. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), lactate dehydrogenase (LDH) measurement, flow cytometry assays were conducted to detect cell proliferation, the release of LDH and cell apoptosis, respectively. The potential relationship between miR-9 and CDK8 was predicted by online database, and confirmed by dual-luciferase reporter assay. We found that miR-9 was increased, while CDK8 was decreased in hypoxia-treated H9c2 cells. miR-9 down-regulation or CDK8 up-regulation promoted cell proliferation, while repressed cell damage and apoptosis in hypoxia-induced H9c2 cells. Moreover, CDK8 was identified to be target of miR-9, and CDK8 knockdown could reverse the effects of miR-9 inhibitor on cell proliferation, damage and apoptosis in hypoxia-treated H9c2 cells. Besides, miR-9 could regulate the Wnt/β-catenin pathway by targeting CDK8 in hypoxic-induced H9c2 cells. In conclusion, miR-9 repressed cell proliferation and promoted cell damage and apoptosis by binding to CDK8 through the Wnt/β-catenin pathway in hypoxic-induced H9c2 cells, which provided a new direction for further studying the treatment of hypoxia-aroused heart diseases.

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Funding

This study was supported by the Hunan Natural Science Foundation Youth Project (No. 2019JJ50845 and NO. 2020JJ5802).

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Correspondence to Juan Duan.

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The present study was approved by the ethical review committee of The Second Xiangya Hospital of Central South University. Written informed consent was obtained from all enrolled patients.

Additional information

Communicated by Sorab Dalal.

Corresponding editor: Sorab Dalal

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Dou, P., Tan, G., Fan, Z. et al. MicroRNA-9 facilitates hypoxia-induced injury and apoptosis in H9c2 cells via targeting CDK8. J Biosci 46, 16 (2021). https://doi.org/10.1007/s12038-020-00126-2

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  • DOI: https://doi.org/10.1007/s12038-020-00126-2

Keywords

  • CDK8
  • H9c2
  • hypoxia
  • miR-9
  • Wnt/β-catenin