LncRNA CAIF inhibits autophagy and attenuates myocardial infarction by blocking p53-mediated myocardin transcription
LncRNA CAIF inhibits autophagy and attenuates myocardial infarction by blocking p53-mediated myocardin transcription
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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塞。
DOI：
10.1038/s41467-017-02280-y
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发表时间：
2018-01-02
影响因子：
16.6
通讯作者：
Wang, Kun
中科院分区：
文献类型：
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作者：
Liu, Cui-Yun;Zhang, Yu-Hui;Wang, Kun
越来越多的证据表明，长链非编码RNA（lncRNA）在各种生物过程中起着至关重要的作用。然而，关于lncRNA对自噬的影响知之甚少。在这里，我们报告，lncRNA，称为心脏自噬抑制因子（CAIF），抑制心脏自噬和减轻心肌梗死靶向p53介导的心肌素转录。过氧化氢和缺血/再灌注时心肌细胞素表达上调，敲低心肌细胞素可抑制自噬并减轻心肌梗死。p53通过调节myocardin表达调控心肌细胞自噬和心肌缺血再灌注损伤。CAIF可直接与p53蛋白结合，阻断p53介导的myocardin转录，导致myocardin表达降低。总的来说，我们的数据揭示了一种新的CAIF-p53-myocardin轴作为心肌细胞自噬的关键调节因子，这将是治疗自噬缺陷相关心血管疾病的潜在治疗靶点。
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.