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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.
Pubmed: (View Article at PubMed) PMID:25504627
DOI: Full-text: DOI:10.1093/cvr/cvu254


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.

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CRRD Object Information
CRRD ID: 13208811
Created: 2017-08-16
Species: All species
Last Modified: 2017-08-16
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.