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

Cui-Yun Liu(Qingdao University), Yu-Hui Zhang(Qingdao University), Ruibei Li(Northwestern University), Lu‐Yu Zhou(Qingdao University), Tao An(Chinese Academy of Medical Sciences & Peking Union Medical College), Rongcheng Zhang(Chinese Academy of Medical Sciences & Peking Union Medical College), Mei Zhai(Chinese Academy of Medical Sciences & Peking Union Medical College), Yan Huang(Chinese Academy of Medical Sciences & Peking Union Medical College), Kaowen Yan(Qingdao University), Yan-Han Dong(Qingdao University), Murugavel Ponnusamy(Qingdao University), Chan Shan(Qingdao University), Sheng Xu(Qingdao University), Qi Wang(Qingdao University), Yanhui Zhang(Qingdao University), Jian Zhang(Chinese Academy of Medical Sciences & Peking Union Medical College), Kun Wang(Qingdao University)
Nature Communications
December 27, 2017
Cited by 341Open Access
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Abstract

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 H 2 O 2 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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