LncRNA CAIF inhibits autophagy and attenuates myocardial infarction by blocking p53-mediated myocardin transcription

LncRNA CAIF 通过阻断 p53 介导的心肌素转录来抑制自噬并减轻心肌梗死

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作者:Cui-Yun Liu, Yu-Hui Zhang, Rui-Bei Li, Lu-Yu Zhou, Tao An, Rong-Cheng Zhang, Mei Zhai, Yan Huang, Kao-Wen Yan, Yan-Han Dong, Murugavel Ponnusamy, Chan Shan, Sheng Xu, Qi Wang, Yan-Hui Zhang, Jian Zhang, Kun Wang

Abstract

Increasing evidence suggests that long noncoding RNAs (lncRNAs) play crucial roles in various biological processes. However, little is known about the effects of lncRNAs on autophagy. Here we report that a lncRNA, termed cardiac autophagy inhibitory factor (CAIF), suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53-mediated myocardin transcription. Myocardin expression is upregulated upon H2O2 and ischemia/reperfusion, and knockdown of myocardin inhibits autophagy and attenuates myocardial infarction. p53 regulates cardiomyocytes autophagy and myocardial ischemia/reperfusion injury by regulating myocardin expression. CAIF directly binds to p53 protein and blocks p53-mediated myocardin transcription, which results in the decrease of myocardin expression. Collectively, our data reveal a novel CAIF-p53-myocardin axis as a critical regulator in cardiomyocyte autophagy, which will be potential therapeutic targets in treatment of defective autophagy-associated cardiovascular diseases.

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