MicroRNA-181c targets Bcl-2 and regulates mitochondrial morphology in myocardial cells.
MicroRNA-181c targets Bcl-2 and regulates mitochondrial morphology in myocardial cells.
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MicroRNA-181c 靶向 Bcl-2 并调节心肌细胞中的线粒体形态
DOI：
10.1111/jcmm.12563
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发表时间：
2015-09
影响因子：
5.3
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Wang H;Li J;Chi H;Zhang F;Zhu X;Cai J;Yang X
细胞凋亡是心力衰竭发生发展的重要机制。线粒体在内源性途径中是执行细胞凋亡的中心。线粒体凋亡途径的主要调节因子是Bcl-2家族，包括促凋亡蛋白和抗凋亡蛋白。MicroRNA是一种非编码小RNA分子，通过抑制mRNA翻译和/或诱导mRNA降解来调节基因表达。已有研究表明microRNA在心血管生理和心血管疾病的发病机制中起着重要作用。我们前期的研究发现，microRNA-181 c是一种在心肌细胞中表达的miRNA，在心力衰竭的发生发展中起着重要作用。通过生物信息学分析，我们预测miR-181 c可以靶向Bcl-2家族中的抗凋亡成员Bcl-2的3′端非翻译区。因此，我们认为miR-181 c参与了Bcl-2的调控。在这项研究中，我们调查了这一假设，使用双荧光素酶报告分析系统。用miR-181 c的模拟物或抑制剂转染培养的心肌细胞。我们发现miR-181 c的水平与Bcl-2蛋白水平呈负相关，并且用miR-181 c的模拟物或抑制剂转染心肌细胞导致这些细胞中caspase、Bcl-2和细胞色素C水平的显著变化。由miR-181 c减少引起的Bcl-2水平增加保护了线粒体形态免受肿瘤坏死因子α诱导的凋亡。
Apoptosis is an important mechanism for the development of heart failure. Mitochondria are central to the execution of apoptosis in the intrinsic pathway. The main regulator of mitochondrial pathway of apoptosis is Bcl-2 family which includes pro- and anti-apoptotic proteins. MicroRNAs are small noncoding RNA molecules that regulate gene expression by inhibiting mRNA translation and/or inducing mRNA degradation. It has been proposed that microRNAs play critical roles in the cardiovascular physiology and pathogenesis of cardiovascular diseases. Our previous study has found that microRNA-181c, a miRNA expressed in the myocardial cells, plays an important role in the development of heart failure. With bioinformatics analysis, we predicted that miR-181c could target the 3′ untranslated region of Bcl-2, one of the anti-apoptotic members of the Bcl-2 family. Thus, we have suggested that miR-181c was involved in regulation of Bcl-2. In this study, we investigated this hypothesis using the Dual-Luciferase Reporter Assay System. Cultured myocardial cells were transfected with the mimic or inhibitor of miR-181c. We found that the level of miR-181c was inversely correlated with the Bcl-2 protein level and that transfection of myocardial cells with the mimic or inhibitor of miR-181c resulted in significant changes in the levels of caspases, Bcl-2 and cytochrome C in these cells. The increased level of Bcl-2 caused by the decrease in miR-181c protected mitochondrial morphology from the tumour necrosis factor alpha-induced apoptosis.