LncRNA TINCR attenuates cardiac hypertrophy by epigenetically silencing CaMKII
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Mingjing Shao1,*, Guangdong Chen2,*, Fengli Lv3, Yanyan Liu4, Hongjun Tian5, Ran Tao6,8, Ronghuan Jiang7,9, Wei Zhang2 and Chuanjun Zhuo2,4,5
1National Integrated Traditional and Western Medicine Center for Cardivascular Disease, China-Japan Friendship Hospital, Beijing, China
2Department of Psychological Medicine, Wenzhou Seventh People’s Hospital, Wenzhou, China
3Department of Rehabilitation, The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
4Department of Psychological Medicine, Tianjin Anning Hospital, Tianjin, China
5Department of Psychological Medicine, Tianjin Anding Hospital, Tianjin, China
6Department of Psychological Medicine, Beijing Shijian Integrated Medicine Science Institute, Beijing, China
7Department of Psychological Medicine, Chinese People’s Liberation Army General Hospital, Beijing, China
8Department of Psychological Medicine, Chinese Land Force General Hospital, Beijing, China
9Department of Psychological Medicine, Chinese People’s Liberation Army, Medical School, Beijing, China
*These authors contributed equally to this work
Chuanjun Zhuo, email: firstname.lastname@example.org
Keywords: TINCR, CaMKII, EZH2, cardiac hypertrophy
Received: March 20, 2017 Accepted: April 26, 2017 Published: May 10, 2017
In the previous study, we established a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC) and found that the expression of long non-coding RNAs TINCR was downregulated in myocardial tissue. The present study was designed to determine the potential role of TINCR in the pathogenesis of cardiac hypertrophy. Our results showed that enforced expression of TINCR could attenuate cardiac hypertrophy in TAC mice. Angiotensin II (Ang-II) was found to be associated with reduced TINCR expression and increased hypertrophy in cultured neonatal cardiomyocytes. RNA-binding protein immunoprecipitation assay confirmed that TINCR could directly bind with EZH2 in cardiomyocytes. The results of chromatin immunoprecipitation assay revealed that EZH2 could directly bind to CaMKII promoter region and mediate H3K27me3 modification. Knockdown of TINCR was found to reduce EZH2 occupancy and H3K27me3 binding in the promoter of CaMKII in cardiomyocytes. In addition, enforced expression of TINCR was found to decrease CaMKII expression and attenuate Ang-II-induced cardiomyocyte hypertrophy. Furthermore, our results also showed that Ang-II could increase CaMKII expression in cardiomyocytes, which consequently contributed to cellular hypertrophy. In conclusion, our findings demonstrated that TINCR could attenuate myocardial hypertrophy by epigenetically silencing of CaMKII, which may provide a novel therapeutic strategy for cardiac hypertrophy.
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