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Abstract：
Background microRNAs (miRNAs) are a class of small, non-coding endogenous RNAs that post-transcriptionally regulate some protein-coding genes. miRNAs play an important role in many cardiac pathophysiological processes, including myocardial infarction, cardiac hypertrophy, and heart failure. miR-499, specifically expressed in skeletal muscle and cardiac cells, is differentially regulated and functions in heart development. However, the function of miR-499 in mature heart is poorly understood. Results We report that cardiac-abundant miR-499 could protect neonatal rat cardiomyocytes against H 2O 2-induced apoptosis. Increased miR-499 level favored survival, while decreased miR-499 level favored apoptosis. We identified three proapoptotic protein-coding genes-Pdcd4, Pacs2, and Dyrk2-as targets of miR-499. miR-499 inhibited cardiomyocyte apoptosis through its suppressive effect on Pdcd4 and Pacs2 expression, thereby blocking Bid expression and BID mitochondrial translocation. We also found that H 2O 2-induced phosphorylation of c-Jun transcriptionally upregulated miR-499 expression via binding of phosphorylated c-Jun to the Myh7b promoter. Conclusions Our results revealed that miR-499 played an inhibiting role in the mitochondrial apoptosis pathway, and had protective effects against H 2O 2-induced injury in cardiomyocytes.
摘要：
背景microRNAs(miRNAs)是一类小,转录后调节一些蛋白质编码基因的非编码内源性RNA。miRNA在许多心脏病理生理过程中发挥重要作用,包括心肌梗塞,心脏肥大,和心力衰竭。miR-499，在骨骼肌和心肌细胞中特异性表达，在心脏发育中受到不同的调节和作用。然而,miR-499在成熟心脏中的功能尚不清楚.结果我们报道了心脏丰富的miR-499可以保护新生大鼠心肌细胞免受H2O2诱导的凋亡。增加的miR-499水平有利于生存，而降低miR-499水平有利于细胞凋亡。我们确定了三个促凋亡蛋白编码基因-Pdcd4，Pacs2和Dyrk2-作为miR-499的靶标。miR-499通过抑制Pdcd4和Pacs2表达抑制心肌细胞凋亡,从而阻断Bid表达和BID线粒体易位。我们还发现H2O2诱导的c-Jun磷酸化通过磷酸化c-Jun与Myh7b启动子的结合转录上调miR-499的表达。结论miR-499在线粒体凋亡通路中起抑制作用,对H2O2诱导的心肌细胞损伤有保护作用。
