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Published on: October 3, 2019
miR-139-5p inhibits isoproterenol-induced cardiac hypertrophy by targetting c-Jun
Su Ming1,2, Wang Shui-Yun3, Qiu Wei4
1Department of Clinical Laboratory, Peking University People's Hospital, Beijing, People's Republic of China suming28@163.com jzwang@hotmail.com.
Insights
MicroRNA-139-5p (miR-139-5p) is down-regulated in hypertrophic cardiomyopathy (HCM). Lower miR-139-5p levels promote cardiac hypertrophy by increasing c-Jun expression, suggesting miR-139-5p is a protective factor.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Biochemistry
Background:
- Hypertrophic cardiomyopathy (HCM) is a genetic heart condition causing cardiac hypertrophy and heart failure.
- Previous studies identified reduced miR-139-5p levels in HCM patients, but its specific role was unknown.
Purpose of the Study:
- To investigate the regulatory role of miR-139-5p in cardiac hypertrophy.
- To elucidate the molecular mechanism by which miR-139-5p influences cardiac hypertrophy.
Main Methods:
- Analysis of miR-139-5p expression in human and mouse cardiac tissues.
- In vitro studies using neonatal rat cardiomyocytes (NRCMs) involving miR-139-5p knockdown and overexpression.
- Investigation of the interaction between miR-139-5p and c-Jun.
Main Results:
- miR-139-5p expression was significantly down-regulated in HCM patient hearts and in mice after transverse aortic constriction (TAC).
- miR-139-5p knockdown in NRCMs induced cardiomyocyte enlargement and increased atrial natriuretic polypeptide (ANP) expression.
- Overexpression of miR-139-5p inhibited isoproterenol (ISO)-induced cardiomyocyte hypertrophy and ANP/brain natriuretic peptide (BNP) expression.
- miR-139-5p directly targets and inhibits c-Jun expression, and c-Jun knockdown attenuated hypertrophy caused by miR-139-5p deficiency.
Conclusions:
- miR-139-5p is downregulated in the hearts of HCM patients.
- miR-139-5p inhibits cardiac hypertrophy, at least partly, by targeting c-Jun.
- miR-139-5p acts as a protective microRNA against cardiac hypertrophy.
Abstract:
Hypertrophic cardiomyopathy (HCM) is a serious monogenic disease characterized by cardiac hypertrophy, fibrosis, sudden cardiac death, and heart failure. Previously, we identified that miR-139-5p was down-regulated in HCM patients. However, the regulatory effects of miR-139-5p remain unclear. Thus, we investigated the role of miR-139-5p in the regulation of cardiac hypertrophy. The expression of miR-139-5p in left ventricular tissues in HCM patients and mice subjected to transverse aortic constriction (TAC) was significantly down-regulated. Knockdown of miR-139-5p expression in neonatal rat cardiomyocytes (NRCMs) induced cardiomyocyte enlargement and increased atrial natriuretic polypeptide (ANP) expression. Overexpression of miR-139-5p antagonized isoproterenol (ISO)-induced cardiomyocyte enlargement and ANP/brain natriuretic peptide (BNP) up-regulation. More importantly, we found that c-Jun expression was inhibited by miR-139-5p in NRCMs. Knockdown of c-Jun expression significantly attenuated cardiac hypertrophy induced by miR-139-5p deprivation. Our data indicated that miR-139-5p was down-regulated in the hearts of HCM patients and that it inhibited cardiac hypertrophy by targetting c-Jun expression.
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