Knockdown of FRAT1 Expression by RNA Interference Inhibits Human Glioblastoma Cell Growth, Migration and Invasion

被引:27
作者
Guo, Geng [1 ]
Kuai, Dong [1 ]
Cai, Sang [2 ]
Xue, Naizhao [1 ]
Liu, Yueting [1 ]
Hao, Jiehe [1 ]
Fan, Yimin [1 ]
Jin, Ji [3 ]
Mao, Xinggang [4 ,5 ]
Liu, Bolin [5 ]
Zhong, Chengliang [6 ]
Zhang, Xiang [5 ]
Yue, Yi [7 ]
Liu, Xiaodong [1 ]
Ma, Ning [1 ]
Guo, Yuhong [1 ]
机构
[1] Shanxi Med Univ, Hosp 1, Dept Neurosurg, Taiyuan, Shanxi Province, Peoples R China
[2] 101 Hosp PLA, Inst Neurosurg, Wuxi, Jiangsu, Peoples R China
[3] Shanxi Med Univ, Taiyuan, Shanxi Province, Peoples R China
[4] PLA 254 Hosp, Dept Neurosurg, Tianjin, Peoples R China
[5] Fourth Mil Med Univ, Xijing Hosp, Dept Neurosurg, Xian 710032, Shaanxi Provinc, Peoples R China
[6] Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Clin Pharmacol Ctr, Tianjin, Peoples R China
[7] Shanxis Gen Hosp Chinese Peoples Armed Police For, Dept Neurosurg, Taiyuan, Shanxi Province, Peoples R China
来源
PLOS ONE | 2013年 / 8卷 / 04期
基金
中国国家自然科学基金;
关键词
BETA-CATENIN; MOLECULAR-CLONING; PATHWAY; AXIN; GBP; OVEREXPRESSION; RECONSTITUTION; PROTOONCOGENE; ACTIVATION; REGULATOR;
D O I
10.1371/journal.pone.0061206
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: FRAT1 positively regulates the Wnt/beta-catenin signaling pathway by inhibiting GSK-3-mediated phosphorylation of beta-catenin. It was originally characterized as a protein frequently rearranged in advanced T cell lymphoma, but has recently also been identified as a proto-oncogene involved in tumorigenesis. Our previous studies showed that FRAT1 was dramatically overexpressed in gliomas and its expression level was significantly increased along with clinicopathological grades. Methods: In the current study, we used RT-PCR and Western blotting to assess the mRNA and protein levels of FRAT1 in three glioma cell lines. In addition, to evaluate its functional role in gliomas, we examined the effects of FRAT1 knockdown on proliferation, migration and invasion in vitro and tumor growth in vivo using glioblastoma U251 cells and RNAi. Results: FRAT1 was highly expressed in all three glioma cell lines. RNAi-mediated down-regulation of endogenous FRAT1 in human glioblastoma U251 cells resulted in suppression of cell proliferation, arrest of cell cycle, inhibition of cell migration and invasion in vitro. Moreover, FRAT1 depletion significantly impaired tumor xenograft growth in nude mice. Conclusions: Our results highlight the potential role of FRAT1 in tumorigenesis and progression of glioblastoma. These findings provide a biological basis for FRAT1 as a potential molecular marker for improved pathological grading and as a novel candidate therapeutic target for glioblastoma management.
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页数:9
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