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Oncotarget. 2017 Apr 25;8(17):28588-28594. doi: 10.18632/oncotarget.15544.

The long non-coding RNA H19 promotes cardiomyocyte apoptosis in dilated cardiomyopathy.

Author information

1
Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
2
Department of Cardiology, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Kunshan, China.
3
Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Abstract

In the previous study, we generated a rat model of dilated cardiomyopathy (DCM) induced by adriamycin and found that the expression of lncRNA H19 was significantly upregulated in myocardial tissue. The present study was aimed to investigate the potential role of H19 in the pathogenesis of adriamycin-induced DCM. H19 knockdown in the myocardium of DCM rats attenuated cardiomyocyte apoptosis and improved left ventricular structure and function. Adriamycin treatment was associated with elevated H19 and miR-675 expression and increased apoptosis in neonatal cardiomyocytes. Enforced expression of miR-675 was found to induce apoptosis in cardiomyocytes with adriamycin treatment and H19-siRNA transfection. The 3'-untranslated region of PA2G4 was cloned downstream of a luciferase reporter construct and cotransfected into HEK293 cells with miR-675 mimic. The results of luciferase assay showed that PA2G4 was a direct target of miR-675. The expression of PA2G4 was reduced in cardiomyocytes transfected with miR-675 mimic. Moreover, H19 knockdown was found to increase PA2G4 expression and suppress apoptosis in cardiomyocytes exposed to adriamycin. In conclusion, our study suggests that H19/miR-675 axis is involved in the promotion of cardiomyocyte apoptosis by targeting PA2G4, which may provide a new therapeutic strategy for the treatment of adriamycin-induced DCM.

KEYWORDS:

H19; PA2G4; apoptosis; dilated cardiomyopathy; miR-675

PMID:
28430627
PMCID:
PMC5438674
DOI:
10.18632/oncotarget.15544
[Indexed for MEDLINE]
Free PMC Article

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