miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy.
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.
Lin
Zhiqiang
Z
Division of Cardiovascular Research, National Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Murtaza
Iram
I
Wang
Kun
K
Jiao
Jianqin
J
Gao
Jie
J
Li
Pei-Feng
PF
D000450:Aldosterone; D000818:Animals; D001483:Base Sequence; D019703:Calcineurin / Q000235:genetics; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D006801:Humans; D007545:Isoproterenol; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014158:Transcription, Genetic; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015854:Up-Regulation
D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; D000070584:Tripartite Motif Proteins; C445503:transcription factor NF-AT c3; D000450:Aldosterone; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; D019703:Calcineurin; D007545:Isoproterenol