The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489.

Abstract:

RATIONALE:Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biological functions and have been extensively investigated in past years. OBJECTIVE:We identified miR-489 and lncRNAs (cardiac hypertrophy related factor, CHRF) from hypertrophic cardiomyocytes. Here, we tested the hypothesis that miR-489 and CHRF can participate in the regulation of cardiac hypertrophy in vivo and in vitro. METHODS AND RESULTS:A microarray was performed to analyze miRNAs in response to angiotensin II treatment, and we found miR-489 was substantially reduced. Enforced expression of miR-489 in cardiomyocytes and transgenic overexpression of miR-489 both exhibited reduced hypertrophic response on angiotensin II treatment. We identified myeloid differentiation primary response gene 88 (Myd88) as a miR-489 target to mediate the function of miR-489 in cardiac hypertrophy. Knockdown of Myd88 in cardiomyocytes and Myd88-knockout mice both showed attenuated hypertrophic responses. Furthermore, we explored the molecular mechanism by which miR-489 expression is regulated and found that an lncRNA that we named CHRF acts as an endogenous sponge of miR-489, which downregulates miR-489 expression levels. CHRF is able to directly bind to miR-489 and regulate Myd88 expression and hypertrophy. CONCLUSIONS:Our present study reveals a novel cardiac hypertrophy regulating model that is composed of CHRF, miR-489, and Myd88. The modulation of their levels may provide a new approach for tackling cardiac hypertrophy.

journal_name

Circ Res

journal_title

Circulation research

authors

Wang K,Liu F,Zhou LY,Long B,Yuan SM,Wang Y,Liu CY,Sun T,Zhang XJ,Li PF

doi

10.1161/CIRCRESAHA.114.302476

subject

Has Abstract

pub_date

2014-04-25 00:00:00

pages

1377-88

issue

9

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.114.302476

journal_volume

114

pub_type

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