Role of microRNA-143 in Fas-mediated apoptosis in human T-cell leukemia Jurkat cells
Role of microRNA-143 in Fas-mediated apoptosis in human T-cell leukemia Jurkat cells
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DOI：
10.1016/j.leukres.2009.04.019
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发表时间：
2009-11-01
影响因子：
2.7
通讯作者：
Naoe, Tomoki
中科院分区：
文献类型：
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作者：
Akao, Yukihiro;Nakagawa, Yoshihito;Naoe, Tomoki
用Fas-activating抗体（CH-11）处理Jurkat T细胞可促进细胞快速死亡，这被证明是半胱氨酸蛋白酶依赖性细胞凋亡。miR-143的表达在细胞凋亡过程中随着时间的延长而上调。miR-143的表达增加出现在处理后1至2 h，此时caspase-8和-3也被激活;并且这种增加几乎被caspase-3或-8抑制剂预处理所抵消。此外，用成熟miR-143转染Jurkat细胞诱导了显著的生长抑制和CH-11诱导的凋亡的增强。相反，在结肠癌DLD-1细胞中被确定为miR-143的靶标的细胞外信号调节蛋白激酶5（ERK 5）在处理后在翻译水平上时间依赖性地下调。在细胞凋亡过程中，FasL的表达水平维持不变，而细胞核内Foxo 3a的表达水平在早期升高。这些数据表明miR-143的上调可能部分通过靶向ERK 5导致Foxo 3a/FasL正反馈环的促进而与凋亡相关。(C)2009爱思唯尔有限公司保留所有权利。
Treatment of Jurkat T cells with Fas-activating antibody (CH-11) facilitated rapid cell death that was shown to be caspase-dependent apoptosis. The expression of miR-143 was up-regulated during the apoptosis with time. The increased expression of miR-143 emerged from 1 to 2 h after the treatment, at which time the caspases-8 and -3 were also activated; and this increase was almost canceled by the pretreatment with an inhibitor of caspase-3 or -8. Furthermore, the transfection of Jurkat cells with mature miR-143 induced a significant growth suppression and enhancement of CH-11-induced apoptosis. On the contrary, an extracellular signal-regulated protein kinase 5 (ERK5), which was determined to be a target of miR-143 in colon cancer DLD-1 cells, was time-dependently down-regulated at the translational level after the treatment. During the apoptosis, the expression level of FasL was maintained and the level of nuclear-Foxo3a was increased in the early phase. These data suggest that the up-regulation of miR-143 could be related to the apoptosis in part by targeting ERK5, which leads to promotion of Foxo3a/FasL positive feedback loop. (C) 2009 Elsevier Ltd. All rights reserved.