Liu Cui-Yun, Zhang Yu-Hui, Li Rui-Bei, Zhou Lu-Yu, An Tao, Zhang Rong-Cheng, Zhai Mei, Huang Yan, Yan Kao-Wen, Dong Yan-Han, Ponnusamy Murugavel, Shan Chan, Xu Sheng, Wang Qi, Zhang Yan-Hui, Zhang Jian, Wang Kun
Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China.
State Key Laboratory of Cardiovascular Disease, Heart Failure center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100037, China.
Nat Commun. 2018 Jan 2;9(1):29. doi: 10.1038/s41467-017-02280-y.
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 HO 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.
越来越多的证据表明,长链非编码RNA(lncRNA)在各种生物学过程中发挥着关键作用。然而,关于lncRNA对自噬的影响知之甚少。在此我们报告一种名为心脏自噬抑制因子(CAIF)的lncRNA,它通过靶向p53介导的心肌肌动蛋白转录来抑制心脏自噬并减轻心肌梗死。在缺氧(HO)和缺血/再灌注时,心肌肌动蛋白的表达上调,而敲低心肌肌动蛋白可抑制自噬并减轻心肌梗死。p53通过调节心肌肌动蛋白的表达来调控心肌细胞自噬和心肌缺血/再灌注损伤。CAIF直接与p53蛋白结合并阻断p53介导的心肌肌动蛋白转录,从而导致心肌肌动蛋白表达降低。总之,我们的数据揭示了一种新的CAIF-p53-心肌肌动蛋白轴作为心肌细胞自噬的关键调节因子,这将成为治疗自噬缺陷相关心血管疾病的潜在治疗靶点。