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


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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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.

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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).

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