Journal
ONCOTARGET
Volume 7, Issue 48, Pages 78331-78342Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13048
Keywords
microRNA-214-3p; cardiac fibrosis; cardiac myofibroblast; EZH1; EZH2; Pathology Section
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Funding
- National Science Foundation of China [81470439, 81270222]
- Scientific Foundations of Guangdong Province [2014A030313635]
- Translational Medicine Foundation of Guangdong General Hospital [2015zh06]
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The role of microRNA-214-3p (miR-214-3p) in cardiac fibrosis was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced cardiac fibrosis. MiR-214-3p was markedly decreased in the fibrotic myocardium of a mouse Ang-II infusion model, but was upregulated in Ang-II-treated mouse myofibroblasts. Cardiac fibrosis was shown attenuated in Ang-II-infused mice received tail vein injection of miR-214-3p agomir. Consistently, miR-214-3p inhibited the expression of Col1a1 and Col3a1 in mouse myofibroblasts in vitro. MiR-214-3p could bind the 3'-UTRs of enhancer of zeste homolog 1 (EZH1) and -2, and suppressed EZH1 and -2 expressions at the transcriptional level. Functionally, miR-214-3p mimic, in parallel to EZH1 siRNA and EZH2 siRNA, could enhance peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression and inhibited the expression of Col1a1 and Col3a1 in myofibroblasts. In addition, enforced expression of EZH1 and -2, and knockdown of PPAR-. resulted in the increase of Col1a1 and Col3a1 in myofibroblasts. Moreover, the NF-kappa B signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in myofibroblasts. Taken together, our results revealed that EZH1 and -2 were novel targets of miR214- 3p, and miR-214-3p might be one potential miRNA for the prevention of cardiac fibrosis.
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