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

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 p...

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Veröffentlicht in:International journal of molecular medicine 2017-06, Vol.39 (6), p.1589-1596
Hauptverfasser: Chen, Zhigang, Zhang, Shaoli, Guo, Changlei, Li, Jianhua, Sang, Wenfeng
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Sprache:eng
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Zusammenfassung: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.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2017.2959