RGD Reference Report - lncRNA H19/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy. - Rat Genome Database

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lncRNA H19/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy.

Authors: Li, Xiangquan  Wang, Hao  Yao, Biao  Xu, Weiting  Chen, Jianchang  Zhou, Xiang 
Citation: Li X, etal., Sci Rep. 2016 Oct 31;6:36340. doi: 10.1038/srep36340.
RGD ID: 156430325
Pubmed: PMID:27796346   (View Abstract at PubMed)
PMCID: PMC5087087   (View Article at PubMed Central)
DOI: DOI:10.1038/srep36340   (Journal Full-text)

We previously established a rat model of diabetic cardiomyopathy (DCM) and found that the expression of lncRNA H19 was significantly downregulated. The present study was designed to investigate the pathogenic role of H19 in the development of DCM. Overexpression of H19 in diabetic rats attenuated oxidative stress, inflammation and apoptosis, and consequently improved left ventricular function. High glucose was associated with reduced H19 expression and increased cardiomyocyte apoptosis. To explore the molecular mechanisms involved, we performed in vitro experiments using cultured neonatal rat cardiomyocytes. Our results showed that miR-675 expression was decreased in cardiomyocytes transfected with H19 siRNA. The 3'UTR of VDAC1 was cloned downstream of a luciferase reporter construct and cotransfected into HEK293 cells with miR-675 mimic. The results of luciferase assay indicated that VDAC1 might be a direct target of miR-675. The expression of VDAC1 was upregulated in cardiomyocytes transfected with miR-675 antagomir, which consequently promotes cellular apoptosis. Moreover, enforced expression of H19 was found to reduce VDAC1 expression and inhibit apoptosis in cardiomyocytes exposed to high glucose. In conclusion, our study demonstrates that H19/miR-675 axis is involved in the regulation of high glucose-induced apoptosis by targeting VDAC1, which may provide a novel therapeutic strategy for the treatment of DCM.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
H19RatDiabetic Cardiomyopathies amelioratesIMP  RGD 
H19MouseDiabetic Cardiomyopathies amelioratesISOH19 (Rattus norvegicus) RGD 
H19HumanDiabetic Cardiomyopathies amelioratesISOH19 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Objects Annotated

Genes (Rattus norvegicus)
H19  (H19 imprinted maternally expressed transcript)

Genes (Mus musculus)
H19  (H19, imprinted maternally expressed transcript)

Genes (Homo sapiens)
H19  (H19 imprinted maternally expressed transcript)


Additional Information