MicroRNA-124 regulates cardiomyocyte apoptosis and myocardial infarction through targeting Dhcr24.
J Mol Cell Cardiol
; 132: 178-188, 2019 07.
Article
en En
| MEDLINE
| ID: mdl-31100313
ABSTRACT
AIMS:
microRNA-124(miR-124) has recently been reported to be elevated in cardiovascular disease. In this study, we aimed to investigate the exact role of miR-124 in cardiomyocytes and myocardial infarction, identifying the functional target and its regulatory mechanisms. METHODS ANDRESULTS:
Cultured cardiomyocytes, myocardial-infarction mouse model, and clinical data were used to study the effects of miR-124 on myocardial ischemia. Expression of miR-124 was up-regulated in H2O2 and hypoxia induced cardiomyocyte injury. miR-124 over-expression significantly increased cardiomyocyte apoptosis, whereas miR-124 inhibition attenuated cell death. 3ß-hydroxysteroid-Delta24 reductase (Dhcr24), a multi-functional enzyme implicated in cholesterol synthesis and various diseases, was identified as a novel functional target of miR-124 in cardiac myocytes. The miR-124-Dhcr24 axis was responsible for cardiomyocyte apoptosis regulation. Furthermore, myocardial infarction induced miR-124 activation and Dhcr24 reduction in vivo. Modulation of miR-124 by intra-myocardial injection of agomiR or antagomiR was capable of manipulating cardiomyocyte apoptosis and myocardial infarction in mice. More importantly, circulating miR-124 was also observed to be elevated in acute myocardial infarction (AMI) patients and was correlated with myocardial injury and cardiac function.CONCLUSION:
Our findings strongly demonstrated that miR-124 targeting Dhcr24 regulates oxidative stress and hypoxia induced cardiomyocyte apoptosis and myocardial infarction. The miR-124-Dhcr24 axis could be a potential biomarker as well as the therapeutic target for AMI.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Apoptosis
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Miocitos Cardíacos
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MicroARNs
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Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH
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Infarto del Miocardio
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Proteínas del Tejido Nervioso
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Mol Cell Cardiol
Año:
2019
Tipo del documento:
Article
País de afiliación:
China