MicroRNA-214 Protects Cardiac Myocytes Against H2O2-Induced Injury
MicroRNA-214 Protects Cardiac Myocytes Against H2O2-Induced Injury
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DOI：
10.1002/jcb.24636
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发表时间：
2014-01-01
影响因子：
4
通讯作者：
Dong, Shimin
中科院分区：
文献类型：
--
作者：
Lv, Guangwei;Shao, Suxia;Dong, Shimin
由多个基因表达水平变化导致的活性氧（ROS）诱导的心肌细胞损伤在众多心脏疾病的发病机制中起着关键作用。本研究的目的是确定微小RNA - 214（miR - 214）在过氧化氢（H₂O₂）介导的心肌细胞基因调控中的潜在作用。在本研究中，我们使用实时定量逆转录聚合酶链反应（qRT - PCR）证明，在用H₂O₂处理后，心肌细胞中的miR - 214表达上调。我们用pre - miR - 214转染细胞以上调miR - 214的表达，并用miR - 214抑制剂（anti - miR - 214）转染细胞以下调miR - 214的表达。通过流式细胞术检测H₂O₂诱导的心肌细胞凋亡。miR - 214抑制剂使凋亡水平升高，而pre - miR - 214使其降低。因此，我们认为miR - 214在H₂O₂诱导的心肌细胞凋亡中起积极作用。第10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）具有组成性活性，被认为是促癌的PI3K/Akt通路的主要下调因子。蛋白质印迹分析显示，在H₂O₂诱导后，心肌细胞中PTEN蛋白的表达降低。Anti - miR - 214增加了PTEN蛋白的表达水平，相反，pre - miR - 214降低了培养的心肌细胞中PTEN蛋白的表达水平。这些结果表明，PTEN受miR - 214调控，并且是心肌细胞中miR - 214的一个重要靶点。总之，miR - 214对H₂O₂刺激敏感，并且miR - 214通过其靶点之一PTEN保护心肌细胞免受H₂O₂诱导的损伤。《细胞生物化学杂志》115: 93 - 101, 2014。（c）2013威利期刊公司
Reactive oxygen species (ROS)-induced cardiac myocyte injury resulting from changes in the expression levels of multiple genes plays a critical role in the pathogenesis of numerous heart diseases. The purpose of this study was to determine the potential roles of microRNA-214 (miR-214) in hydrogen peroxide (H2O2)-mediated gene regulation in cardiac myocytes. In this study, we used quantitative real-time RT-PCR (qRT-PCR) to demonstrate that miR-214 was upregulated in cardiac myocytes after treatment with H2O2. We transfected cells with pre-miR-214 to upregulate miR-214 expression and transfected cells with a miR-214 inhibitor (anti-miR-214) to downregulate miR-214 expression. H2O2-induced cardiac cell apoptosis was detected by flow cytometry. The level of apoptosis was increased by the miR-214 inhibitor and decreased by pre-miR-214. Therefore, we believe that miR-214 plays a positive role in H2O2-induced cardiac cell apoptosis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is constitutively active and is considered to be the primary downregulator of the pro-oncogenic PI3K/Akt pathway. Western blot analysis revealed that the expression of the PTEN protein in cardiac myocytes decreased after H2O2 induction. Anti-miR-214 increased PTEN protein expression level, in contrast, pre-miR-214 decreased the PTEN protein expression level in cultured cardiac myocytes. These results indicate that PTEN is regulated by miR-214 and serves as an important target of miR-214 in cardiac myocytes. In conclusion, miR-214 is sensitive to H2O2 stimulation, and miR-214 protects cardiac myocytes against H2O2-induced injury via one of its targets, PTEN. J. Cell. Biochem. 115: 93-101, 2014. (c) 2013 Wiley Periodicals, Inc.