Journal Article

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

Mengwen Yan, Chen Chen, Wei Gong, Zhongwei Yin, Ling Zhou, Sandip Chaugai and Dao Wen Wang

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 105, issue 3, pages 340-352
Published in print March 2015 | ISSN: 0008-6363
Published online December 2014 | e-ISSN: 1755-3245 | DOI: https://dx.doi.org/10.1093/cvr/cvu254
miR-21-3p regulates cardiac hypertrophic response by targeting histone deacetylase-8

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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-Gsk3β expression.

Conclusion

Our data reveal a role of miR-21-3p in regulating HDAC8 expression and Akt/Gsk3β pathway, and suggest that modulation of miR-21-3p levels may provide a therapeutic approach for cardiac hypertrophy.

Keywords: Cardiac hypertrophy; miRNA; HDAC

Journal Article.  7358 words.  Illustrated.

Subjects: Cardiovascular Medicine

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