miR-218 Involvement in Cardiomyocyte Hypertrophy Is Likely through Targeting REST.
MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with significant risks of heart failure. However, many microRNAs are still not recognized for their functions in pathophysiological processes. In this study, we evaluated effects of miR-218 in cardiomyocyte hypertrophy using both in vitro and in vivo models. We found that miR-218 was evidently downregulated in a transverse aortic constriction (TAC) mouse model. Overexpression of miR-218 is sufficient to reduce hypertrophy, whereas the suppression of miR-218 aggravates hypertrophy in primary cardiomyocytes induced by isoprenaline (ISO). In addition, we identified RE1-silencing transcription factor (REST) as a novel target of miR-218; it negatively regulated the expression of REST in hypertrophic cardiomyocytes and the TAC model. These results showed that miR-218 plays a crucial role in cardiomyocyte hypertrophy, likely via targeting REST, suggesting a potential candidate target for interfering hypertrophy.
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. ljjdaisywin@163.com.
Jing-Jing
JJ
Liu
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. zhaocuimei2000@126.com.
Cui-Mei
CM
Zhao
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. happylag5@163.com.
Zhi-Gang
ZG
Li
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. 14wang_yumei@tongji.edu.cn.
Yu-Mei
YM
Wang
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. wikimiao@126.com.
Wei
W
Miao
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. wuxiujuan1992@163.com.
Xiu-Juan
XJ
Wu
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. 2015vivian_wang@tongji.edu.cn.
Wen-Jing
WJ
Wang
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. linuxonly@163.com.
Chang
C
Liu
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. wangduotc@126.com.
Duo
D
Wang
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. tongji_wk@163.com.
Kang
K
Wang
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. lilirz@tongji.edu.cn.|Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. lilirz@tongji.edu.cn.|Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China. lilirz@tongji.edu.cn.
Li
L
Li
Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, China. luyingpeng@tongji.edu.cn.|Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. luyingpeng@tongji.edu.cn.|Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China. luyingpeng@tongji.edu.cn.
Lu-Ying
LY
Peng
D000818:Animals; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000139:chemically induced / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D007545:Isoproterenol / Q000009:adverse effects*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction; D000099229:RE1-Silencing Transcription Factor
D007545:Isoproterenol; D035683:MicroRNAs; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C550324:Mirn128 microRNA, mouse
REST; cardiomyocyte; hypertrophy; miR-218