Fbxw8 is involved in the proliferation of human choriocarcinoma JEG-3 cells
Fbxw8 is involved in the proliferation of human choriocarcinoma JEG-3 cells
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Fbxw8参与人绒毛膜癌JEG-3细胞的增殖
DOI：
10.1007/s11033-010-0288-7
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发表时间：
2011-03-01
影响因子：
2.8
通讯作者：
Yu, Xiaoguang
中科院分区：
文献类型：
--
作者：
Lin, Ping;Fu, Jiejun;Yu, Xiaoguang
Fbxw8是一个类似SCF的E3泛素连接酶复合体的F-box成分。缺乏Fbxw8的小鼠在胎盘和胚胎中表现出类似于胎儿生长迟缓的病理缺陷，提示Fbxw8在胎盘形成中起作用。滋养层细胞的增殖能力在胎盘发育中非常重要。在此背景下，我们发现Fbxw8在四个不同的人滋养层细胞系中都有表达。SiRNA沉默Fbxw8的表达可抑制绒癌JEG-3细胞的生长。通过Western blotting、细胞周期分析，我们发现RNAi通过下调CDK1、CDK2、Cyclin A和Cyclin B1的表达，上调p27的表达，诱导细胞生长停滞于G2/M期。相反，Fbxw8的过度表达导致了相反的效果。这些结果表明，Fbxw8通过调控CDK1、CDK2、Cyclin A、Cyclin B1和p27的表达，通过G2/M期转变对人滋养层细胞，特别是JEG-3细胞的增殖起重要作用。
Fbxw8 is the F-box component of a SCF-like E3 ubiquitin ligase complex. Mice lacking Fbxw8 exhibit pathological defects in placenta and embryo similar to fetal growth retardation, suggesting a role of Fbxw8 in placentation. Proliferative capacity of trophoblast cells is very important in placental development. In this context, we revealed that Fbxw8 was expressed in four different human trophoblast cell lines. Silencing of Fbxw8 expression by siRNA inhibited the growth of choriocarcinoma JEG-3 cells. By Western blotting, cell cycle analysis, we showed that down-regulation of Fbxw8 by RNAi induced cell-growth arrest at G2/M phase through decreasing the levels of CDK1, CDK2, cyclin A and cyclin B1 and up-regulation of p27 at protein level. Conversely, over-expression of Fbxw8 led to the opposite effect. These results suggest that Fbxw8 plays an essential role in the proliferation of human trophoblast cells, especially JEG-3 cells, via G2/M phase transition in association with regulation of CDK1, CDK2, cyclin A, cyclin B1 and p27 expression.