miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy
- 21 July 2009
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 106 (29), 12103-12108
- https://doi.org/10.1073/pnas.0811371106
Abstract
Cardiac hypertrophy is accompanied by maladaptive cardiac remodeling, which leads to heart failure or sudden death. MicroRNAs (miRNAs) are a class of small, noncoding RNAs that mediate posttranscriptional gene silencing. Recent studies show that miRNAs are involved in the pathogenesis of hypertrophy, but their signaling regulations remain to be understood. Here, we report that miR-23a is a pro-hypertrophic miRNA, and its expression is regulated by the transcription factor, nuclear factor of activated T cells (NFATc3). The results showed that miR-23a expression was up-regulated upon treatment with the hypertrophic stimuli including isoproterenol and aldosterone. Knockdown of miR-23a could attenuate hypertrophy, suggesting that miR-23a is able to convey the hypertrophic signal. In exploring the molecular mechanism by which miR-23a is up-regulated, we identified that NFATc3 could directly activate miR-23a expression through the transcriptional machinery. The muscle specific ring finger protein 1, an anti-hypertrophic protein, was identified to be a target of miR-23a. Its translation could be suppressed by miR-23a. Our data provide a model in which the miRNA expression is regulated by the hypertrophic transcriptional factor.Keywords
This publication has 38 references indexed in Scilit:
- Taking microRNAs to heartTrends in Molecular Medicine, 2008
- Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430Science, 2007
- MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targetsJCI Insight, 2007
- MicroRNAs in the Human HeartCirculation, 2007
- Signaling pathways mediating cardiac myocyte gene expression in physiological and stress responsesJournal of Cellular Physiology, 2007
- MicroRNA-133 controls cardiac hypertrophyNature Medicine, 2007
- Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNAScience, 2007
- Muscle Ring Finger 1, but not Muscle Ring Finger 2, Regulates Cardiac Hypertrophy In VivoCirculation Research, 2007
- TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodelingJCI Insight, 2006
- TGFβ inducible early gene‐1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathwayJournal of Cellular Biochemistry, 2006