Research Papers: Pathology:

Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts

Wen-Si Zhu, Chun-Mei Tang, Zhen Xiao, Jie-Ning Zhu, Qiu-Xiong Lin, Yong-Heng Fu, Zhi-Qin Hu, Zhuo Zhang, Min Yang, Xi-Long Zheng, Shu-Lin Wu and Zhi-Xin Shan _

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Oncotarget. 2016; 7:78331-78342. https://doi.org/10.18632/oncotarget.13048

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Wen-Si Zhu1,2,*, Chun-Mei Tang2,3,*, Zhen Xiao1,2,*, Jie-Ning Zhu1,2, Qiu-Xiong Lin1,2, Yong-Heng Fu1,2, Zhi-Qin Hu2,3, Zhuo Zhang2,4, Min Yang1,2, Xi-Long Zheng5, Shu-Lin Wu1,2 and Zhi-Xin Shan1,2

1 Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China

2 Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

3 Southern Medical University, Guangzhou, China

4 School of Medicine, South China University of Technology, Guangzhou, China

5 The Libin Cardiovascular Institute of Alberta, Department of Biochemistry & Molecular Biology, The University of Calgary, Calgary, Canada

* These authors have contributed equally to this work

Correspondence to:

Zhi-Xin Shan, email:

Keywords: microRNA-214-3p, cardiac fibrosis, cardiac myofibroblast, EZH1, EZH2, Pathology Section

Received: August 31, 2016 Accepted: October 28, 2016 Published: November 03, 2016


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-γ (PPAR-γ) expression and inhibited the expression of Col1a1 and Col3a1 in myofibroblasts. In addition, enforced expression of EZH1 and -2, and knockdown of PPAR-γ resulted in the increase of Col1a1 and Col3a1 in myofibroblasts. Moreover, the NF-κB 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 miR-214-3p, and miR-214-3p might be one potential miRNA for the prevention of cardiac fibrosis.

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