The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes (Retracted article. See vol. 124, pg. 3187, 2011)
The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes (Retracted article. See vol. 124, pg. 3187, 2011)
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DOI：
10.1242/jcs.010728
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发表时间：
2007-09-01
影响因子：
4
通讯作者：
Yang, Baofeng
中科院分区：
文献类型：
--
作者：
Xu, Chaoqian;Lu, Yanjie;Yang, Baofeng
microrna miR-1和miR-133在心脏和骨骼肌中优先表达，并已被证明调节这些细胞的分化和增殖。我们在这里报告了miR-1和miR-133调节心肌细胞凋亡的细胞功能的一个新方面。miR-1和miR-133在氧化应激诱导的H9c2大鼠心室细胞凋亡中产生相反的作用，miR-1是促凋亡的，miR-133是抗凋亡的。miR-1水平在氧化应激下显著升高。我们仅在HSP60和HSP70基因的3 '-非翻译区鉴定了miR-1的单一靶点，并在caspase-9基因的整个序列中鉴定了miR-133的多个假定靶点。miR-1降低了HSP60和HSP70蛋白的水平，而不改变其转录水平，而miR-133完全不影响HSP60和HSP70的表达。相比之下，miR-133在蛋白和mRNA水平上抑制caspase-9的表达。荧光素酶报告基因实验进一步证实了HSP60、HSP70和caspase-9的转录后抑制作用。我们的研究结果表明，miR-1和miR-133参与调节细胞命运，miR-1和/或miR-133水平的增加和/或降低有利于细胞凋亡，miR-1和/或miR-133水平的降低有利于细胞存活。miR-1转录后抑制HSP60和HSP70， miR133转录后抑制caspase-9，这对它们的拮抗作用有重要作用。
The microRNAs miR-1 and miR-133 are preferentially expressed in cardiac and skeletal muscles and have been shown to regulate differentiation and proliferation of these cells. We report here a novel aspect of cellular function of miR-1 and miR-133 regulation of cardiomyocyte apoptosis. miR-1 and miR-133 produced opposing effects on apoptosis, induced by oxidative stress in H9c2 rat ventricular cells, with miR-1 being pro-apoptotic and miR-133 being antiapoptotic. miR-1 level was significantly increased in response to oxidative stress. We identified single target sites for miR-1 only, in the 3 '- untranslated regions of the HSP60 and HSP70 genes, and multiple putative target sites for miR-133 throughout the sequence of the caspase-9 gene. miR-1 reduced the levels of HSP60 and HSP70 proteins without changing their transcript levels, whereas miR-133 did not affect HSP60 and HSP70 expression at all. By contrast, miR-133 repressed caspase-9 expression at both the protein and mRNA levels. The post-transcriptional repression of HSP60 and HSP70 and caspase-9 was further confirmed by luciferase reporter experiments. Our results indicate that miR-1 and miR-133 are involved in regulating cell fate with increased miR-1 and/or decreased miR-133 levels favoring apoptosis and decreased miR-1 and/or miR133 levels favoring survival. Post-transcriptional repression of HSP60 and HSP70 by miR-1 and of caspase-9 by miR133 contributes significantly to their opposing actions.