miR-133a mediates the hypoxia-induced apoptosis by inhibiting TAGLN2 expression in cardiac myocytes
miR-133a mediates the hypoxia-induced apoptosis by inhibiting TAGLN2 expression in cardiac myocytes
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DOI：
10.1007/s11010-014-2273-2
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发表时间：
2015-02-01
影响因子：
4.3
通讯作者：
Yang, Kan
中科院分区：
文献类型：
--
作者：
Li, An-ying;Yang, Qiong;Yang, Kan
心肌缺氧会引发细胞损伤和凋亡，是导致心功能障碍的主要原因。失调的 microRNA 及其在心肌细胞凋亡中的作用引起了广泛关注。 miR-133a 是正常心脏中最丰富的 miRNA 之一，在缺氧应激下观察到 miR-133a 表达的显着变化。然而，这种microRNA在心肌缺氧诱导的细胞凋亡中的作用目前尚不清楚。在本研究中，我们发现缺氧的H9c2细胞中miR-133a的表达下调，并且其表达随着缺氧时间的延长而逐渐降低。功能分析显示 miR-133a 减弱缺氧诱导的细胞凋亡。我们进一步检测了凋亡相关蛋白的表达。结果显示，miR-133a显着抑制凋亡蛋白caspase-8、caspase-9和caspase-3的表达，同时提高Bcl-2的表达。生物信息学分析结合双荧光素酶报告基因分析，确定 miR-133a 直接与 TAGLN2 mRNA 的 3'-非翻译区 (3'-UTR) 结合，并在转录和翻译水平抑制表达。接下来，利用TAGLN2敲除揭示TAGLN2通过caspase-8凋亡途径调节缺氧诱导的细胞凋亡。综上所述，我们的数据证明了 miR-133a 在缺氧诱导的细胞凋亡中的作用，并暗示其在心功能障碍治疗中的潜力。
Myocardial hypoxia is a major cause of cardiac dysfunction due to its triggering cell injury and apoptosis. Deregulated microRNAs and their roles in cardiomyocyte apoptosis have attracted much attention. miR-133a is among the most abundant of the miRNAs present in the normal heart, and significant changes in expression of miR-133a were observed in response to anoxia stress. However, the role of this microRNA in myocardial hypoxia-induced apoptosis is presently unclear. In this study, we identified that miR-133a expression was down-regulated in hypoxic H9c2 cells, and its expression gradually decreased with hypoxia time. Functional analysis revealed that miR-133a attenuated hypoxia-induced apoptosis. We further detected expression of apoptosis-related proteins. The results showed that miR-133a suppressed the expression of apoptotic proteins caspase-8, caspase-9, and caspase-3 significantly, while improved the expression of Bcl-2. Bioinformatics analysis, combined with dual-luciferase reporter analysis, was applied to determine that miR-133a directly was binded to the 3'-untranslated region (3'-UTR) of TAGLN2 mRNA and suppressed expression at both transcriptional and translational levels. Next, TAGLN2 knockout was used to reveal that TAGLN2 modulated hypoxia-induced apoptosis via caspase-8 apoptotic pathway. Taken together, our data demonstrated the roles of miR-133a in hypoxia-induced apoptotic and implicate its potential in cardiac dysfunctions therapy.