CARL lncRNA 通过抑制 miR-539 依赖的 PHB2 下调来抑制心肌细胞缺氧诱导的线粒体分裂和凋亡。
CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation.
机构信息
1] Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2].
1] Department of Pharmacology, University of California, Irvine, California 92697, USA [2].
出版信息
Nat Commun. 2014 Apr 7;5:3596. doi: 10.1038/ncomms4596.
Abnormal mitochondrial fission participates in the pathogenesis of many diseases. Long non-coding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the regulation of mitochondrial network is unclear. Here we report that a lncRNA, named cardiac apoptosis-related lncRNA (CARL), can suppress mitochondrial fission and apoptosis by targeting miR-539 and PHB2. The results show that PHB2 is able to inhibit mitochondrial fission and apoptosis. miR-539 is responsible for the dysfunction of PHB2 and regulates mitochondrial fission and apoptosis by targeting PHB2. Further, we show that CARL can act as an endogenous miR-539 sponge that regulates PHB2 expression, mitochondrial fission and apoptosis. Our present study reveals a model of mitochondrial fission regulation that is composed of CARL, miR-539 and PHB2. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction.
异常的线粒体裂变参与了许多疾病的发病机制。长链非编码 RNA（lncRNA）作为基因调控的新成员不断涌现，但 lncRNA 如何调节线粒体网络尚不清楚。在这里，我们报告了一种 lncRNA，命名为心脏细胞凋亡相关 lncRNA（CARL），可以通过靶向 miR-539 和 PHB2 来抑制线粒体裂变和细胞凋亡。结果表明，PHB2 能够抑制线粒体裂变和细胞凋亡。miR-539 负责 PHB2 的功能障碍，并通过靶向 PHB2 来调节线粒体裂变和细胞凋亡。此外，我们发现 CARL 可以作为内源性 miR-539 海绵，调节 PHB2 的表达、线粒体裂变和细胞凋亡。我们的研究揭示了一个由 CARL、miR-539 和 PHB2 组成的线粒体裂变调节模型。调节它们的水平可能为解决细胞凋亡和心肌梗死提供一种新方法。
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