RGD Reference Report - miR-21-3p regulates cardiac hypertrophic response by targeting histone deacetylase-8. - Rat Genome Database

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miR-21-3p regulates cardiac hypertrophic response by targeting histone deacetylase-8.

Authors: Yan, Mengwen  Chen, Chen  Gong, Wei  Yin, Zhongwei  Zhou, Ling  Chaugai, Sandip  Wang, Dao Wen 
Citation: Yan M, etal., Cardiovasc Res. 2015 Mar 1;105(3):340-52. doi: 10.1093/cvr/cvu254. Epub 2014 Dec 10.
RGD ID: 13208811
Pubmed: PMID:25504627   (View Abstract at PubMed)
DOI: DOI:10.1093/cvr/cvu254   (Journal Full-text)


AIMS: Growing evidences indicate that microRNAs (miRNAs) are involved in cardiac hypertrophy development. Multiple miRNAs have been identified as diagnostic and prognostic biomarkers of cardiac hypertrophy, as well as potential therapeutic tools. The present study aimed to investigate the functions and regulatory mechanisms of miR-21-3p in cardiac hypertrophy.
METHODS AND RESULTS: Decreased expression of miR-21-3p was observed in cardiac hypertrophy induced by transverse aortic constriction (TAC) and angiotensin (Ang) II infusion in mice. To further explore the role of miR-21-3p in cardiac hypertrophy, rAAV-miR-21-3p was administered intravenously in mice. Overexpression of miR-21-3p markedly suppressed TAC-induced cardiac hypertrophy and also blocked Ang II-induced cardiac hypertrophy as determined by cardiac function measurement and biomarker detection. Furthermore, western blot assays showed that histone deacetylase-8 (HDAC8) was silenced by miR-21-3p, and luciferase reporter assays showed that miR-21-3p binds to the 3' UTR of HDAC8. Moreover, re-expression of HDAC8 attenuated miR-21-3p-mediated suppression of cardiac hypertrophy by enhancing phospho-Akt and phospho-Gsk3ß expression.
CONCLUSION: Our data reveal a role of miR-21-3p in regulating HDAC8 expression and Akt/Gsk3ß pathway, and suggest that modulation of miR-21-3p levels may provide a therapeutic approach for cardiac hypertrophy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly treatmentISOHdac8 (Mus musculus)13208811; 13208811 RGD 
Cardiomegaly treatmentIEP 13208811 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdac8  (histone deacetylase 8)

Genes (Mus musculus)
Hdac8  (histone deacetylase 8)

Genes (Homo sapiens)
HDAC8  (histone deacetylase 8)


Additional Information