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.

Bioscience Reports
|February 15, 2018
PubMed

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.

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