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首页> 外文期刊>Cell biology international. >MiR-92a mediates AZD6244 induced apoptosis and G1-phase arrest of lymphoma cells by targeting Bim.
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MiR-92a mediates AZD6244 induced apoptosis and G1-phase arrest of lymphoma cells by targeting Bim.

机译：MiR-92a通过靶向Bim介导AZD6244诱导的淋巴瘤细胞凋亡和G1期阻滞。

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摘要

AZD6244, an ATP-uncompetitive inhibitor of mitogen-activated protein kinase 1/2 (MEK1/2), has shown activity in several malignant tumours. However, whether AZD6244 has a function in lymphoma cells is not known. We report that AZD6244 treatment represses the growth of Raji and MOLT4 cells by inducing apoptosis and G1-phase arrest. Using miRNAs array and quantitative RT-PCR, miR-92a was downregulated byAZD6244 treatment through the ERK1/2-AP1 signalling pathway. Overexpression of miR-92a abrogated AZD6244-induced apoptosis and G1-phase arrest, indicating that it is involved in the cytotoxicity of AZD6244 in lymphoma cells. A luciferase reporter assay showed that miR-92a directly targetsthe 3'-UTRs of Bim. Overexpression of miR-92a mimics downregulated Bim mRNA and protein expression level, indicating that miR-92a negatively regulates its expression at both levels. Silencing Bim decreases AZD6244-induced apoptosis and G1-phase arrest, suggesting that Bim contributes to the growth arrest. Thus, miR-92a mediates AZD6244-induced cytotoxicity of lymphoma cells by targeting Bim. Downregulation of miR-92a by AZD6244 is mediated by the ERK1/2-AP1 signalling pathway.
机译：AZD6244是一种有丝分裂原激活的蛋白激酶1/2（MEK1 / 2）的非ATP竞争性抑制剂，在几种恶性肿瘤中均具有活性。但是，AZD6244是否在淋巴瘤细胞中具有功能尚不清楚。我们报告说，AZD6244治疗通过诱导凋亡和G1期阻滞来抑制Raji和MOLT4细胞的生长。使用miRNA阵列和定量RT-PCR，通过ERK1 / 2-AP1信号通路的AZD6244处理下调了miR-92a。 miR-92a的过表达消除了AZD6244诱导的细胞凋亡和G1期阻滞，表明它参与了AZD6244在淋巴瘤细胞中的细胞毒性作用。荧光素酶报告基因测定表明，miR-92a直接靶向Bim的3'-UTR。 miR-92a的过表达模拟了Bim mRNA和蛋白表达水平的下调，表明miR-92a在这两个水平上均负调节其表达。沉默Bim可减少AZD6244诱导的细胞凋亡和G1期阻滞，提示Bim有助于生长阻滞。因此，miR-92a通过靶向Bim介导AZD6244诱导的淋巴瘤细胞的细胞毒性。 AZD6244对miR-92a的下调是由ERK1 / 2-AP1信号通路介导的。

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