Downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4

Chen,Zhigang; Zhang,Shaoli; Guo,Changlei; Li,Jianhua; Sang,Wenfeng

doi:10.3892/ijmm.2017.2959

Downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4

Authors:
- Zhigang Chen
- Shaoli Zhang
- Changlei Guo
- Jianhua Li
- Wenfeng Sang
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Internal Medicine Nursing, College of Nursing, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
Published online on: April 20, 2017 https://doi.org/10.3892/ijmm.2017.2959
Pages: 1589-1596

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Abstract

Hypoxia-induced cardiomyocyte apoptosis plays an important role in the development of ischemic heart disease. MicroRNAs (miRNAs or miRs) are emerging as critical regulators of hypoxia-induced cardiomyocyte apoptosis. miR-200c is an miRNA that has been reported to be related to apoptosis in various pathological processes; however, its role in hypoxia‑induced cardiomyocyte apoptosis remains unclear. In the present study, we aimed to investigate the potential role and underlying mechanism of miR-200c in regulating hypoxia‑induced cardiomyocyte apoptosis. We found that miR-200c was significantly upregulated by hypoxia in cardiomyocytes, as detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The lactate dehydrogenase, MTT, Annexin V/propidium iodide apoptosis and caspase-3 activity assays showed that downregulation of miR-200c markedly improved cell survival and suppressed the apoptosis of cardiomyocytes in response to hypoxia. Bioinformatics analysis and the dual-luciferase reporter assay demonstrated that miR-200c directly targeted the 3'-untranslated region of GATA-4, an important transcription factor for cardiomyocyte survival. RT-qPCR and western blot analysis showed that suppression of miR-200c significantly increased GATA-4 expression. Furthermore, downregulation of miR-200c upregulated the expression of the anti-apoptotic gene Bcl-2. However, the protective effects against hypoxia induced by the downregulation of miR‑200c were significantly abolished by GATA-4 knockdown. Taken together, our results suggest that downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4, providing a potential therapeutic molecular target for the treatment of ischemic heart disease.

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