Research Papers:

LncRNA H19 inhibits autophagy by epigenetically silencing of DIRAS3 in diabetic cardiomyopathy

Chuanjun Zhuo, Ronghuan Jiang, Xiaodong Lin and Mingjing Shao _

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Oncotarget. 2017; 8:1429-1437. https://doi.org/10.18632/oncotarget.13637

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Chuanjun Zhuo1,2,3,4,*, Ronghuan Jiang5,* Xiaodong Lin1, Mingjing Shao6

1Department of Psychological Medicine, Wenzhou Seventh People’s Hospital, Wenzhou, China

2Institute of Mental Health, Jining Medical University, Jining, China

3Department of Psychological Medicine, Tianjin Anding Hospital, Tianjin, China

4Department of Psychological Medicine, Tianjin Anning Hospital, Tianjin, China

5Department of Psychological Medicine, Chinese People’s Liberation Army (PLA) General Hospital, Chinese PLA (People’s Liberation Army) Medical School, Beijing, China

6Department of Cardiology, China-Japan Friendship Hospital, Beijing, China

*These authors contributed equally to this work

Correspondence to:

Chuanjun Zhuo, email: [email protected]

Mingjing Shao, email: [email protected]

Keywords: H19, DIRAS3, autophagy, diabetic cardiomyopathy

Received: October 07, 2016    Accepted: November 04, 2016    Published: November 26, 2016


We previously generated a rat model of diabetic cardiomyopathy and found that the expression of long non-coding RNA H19 was downregulated. The present study was aimed to explore the pathogenic role of H19 in the development of diabetic cardiomyopathy. Overexpression of H19 in diabetic rats attenuated cardiomyocyte autophagy and improved left ventricular function. High glucose was found to reduce H19 expression and increase autophagy in cultured neonatal cardiomyocytes. The results of RNA-binding protein immunoprecipitation showed that H19 could directly bind with EZH2 in cardiomyocytes. The chromatin immunoprecipitation assays indicated that H19 knockdown could reduce EZH2 occupancy and H3K27me3 binding in the promoter of DIRAS3. In addition, overexpression of H19 was found to downregulate DIRAS3 expression, promote mTOR phosphorylation and inhibit autophagy activation in cardiomyocytes exposed to high glucose. Furthermore, we also found that high glucose increased DIRAS3 expression in cardiomyocytes and DIRAS3 induced autophagy by inhibiting mTOR signaling. In conclusion, our study suggested that H19 could inhibit autophagy in cardiomyocytes by epigenetically silencing of DIRAS3, which might provide novel insights into understanding the molecular mechanisms of diabetic cardiomyopathy.

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