PI3K／AKT信号通路调控MKP3表达促进胶质母细胞瘤细胞增殖的实验研究#br#

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摘要/Abstract

摘要： 目的探讨MKP3在胶质母细胞瘤（GBM）中表达以及MKP3高表达对GBM细胞增殖的影响及其分子作用机制。
方法利用TCGA数据库分析GBM中MKP3表达及不同MKP3表达患者的生存情况；选取GBM细胞U87 MG分别转染siMKP3和siNC，利用MTT实验和EdU法流式细胞术检测U87 MG细胞增殖的变化情况；Western blotting检测pAKT、AKT、MKP3及GAPDH的蛋白表达； 1 μmol／L PI3K特异性抑制剂以及pCDHMKP3过表达质粒验证PI3K／AKTMKP3轴在U87 MG细胞增殖中的作用。
结果TCGA数据库分析显示，GBM组织中的MKP3表达显著高于正常组织，差异有统计学意义（P＜005）；MKP3高表达患者生存率显著低于MKP3低表达患者，差异亦有统计学意义（P＜005）。 MTT法结果显示，siMKP3组细胞增殖活力为0431±0116，显著低于SiNC组的0986±0056（P＜005）。EdU法结果显示，沉默MKP3表达可显著抑制U87 MG细胞的增殖。PI3K／AKT信号通路抑制能够明显阻滞U87 MG细胞的增殖，过表达MKP3后可使 U87 MG细胞增殖能力基本恢复。过表达MKP3并不会引起AKT的磷酸化增加。
结论PI3K／AKT信号通路通过上调MKP3表达可以诱导U87 MG细胞增殖，促进GBM发生发展。

关键词: 胶质母细胞瘤, MKP3, PI3K／AKT, 增殖

Abstract: ObjectiveTo investigate the expression of MKP3 in glioblastoma （GBM） and the effect of MKP3 overexpression on GBM cell proliferation and its possible molecular mechanism.
MethodsTCGA database was used to analyze the expression of MKP3 in GBM and the survival of patients with different MKP3 expression. U87 MG cells was transfected with siMKP3 and siNC. The proliferation of glioblastoma U87 MG cell line was detected by MTT assay and EdU flow cytometry. Western blotting was used to detect the protein expression of pAKT， AKT， MKP3 and GAPDH. The role of PI3K／AKTMKP3 axis in the proliferation of glioblastoma was determined by a 1 μmol／L PI3K specific inhibitor and a pCDHMKP3 overexpression plasmid.
ResultsThe analysis of TCGA database showed that the expression of MKP3 in GBM was significantly higher than that of normal tissue， and the difference was statistically significant （P＜005）； and the survival rate of patients with MKP3 high expression was significantly lower than that of patients with MKP3 low expression， and the difference was statistically significant （P＜005）. The MTT assay showed that the cell proliferation activity of the MKP3 expression silencing group was （0431±0116） significantly lower than that of the NC group （0986 ± 0056）， and the difference was statistically significant （P＜005）. The results of EdU showed that silencing MKP3 expression significantly inhibited the proliferation of U87 MG cells. Inhibition of PI3K／AKT signaling pathway can significantly block the proliferation of U87 MG cells. After overexpressed MKP3， the proliferation ability of U87 MG cells basically recovered. Overexpression of MKP3 did not increase the phosphorylation of AKT.
ConclusionPI3K／AKT signaling pathway can promote the proliferation of GBM cells and increase the development of glioblastoma by up regulating MKP3 expression.

Key words: Glioblastoma（GBM）, MKP3, PI3K／AKT, Proliferation

侯兵, 郭志旺, 周涛, 吴涛. PI3K／AKT信号通路调控MKP3表达促进胶质母细胞瘤细胞增殖的实验研究#br#

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[J]. 临床肿瘤学杂志, 2018, 23(7): 577-581.

HOU Bing, GUO Zhiwang, ZHOU Tao, WU Tao. . PI3K／AKT signaling pathway promotes proliferation of glioblastoma cells via upregulating MKP3 expression#br#

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[J]. Chinese Clinical Oncology, 2018, 23(7): 577-581.

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