Efficient Inhibition of Human Glioma Development by RNA Interference-Mediated Silencing of PAK5

被引:20
|
作者
Gu, Xuefeng [1 ,2 ]
Wang, Ce [3 ]
Wang, Xuefeng [3 ]
Ma, Guoda [1 ]
Li, You [2 ]
Cui, Lili [1 ]
Chen, Yanyan [2 ]
Zhao, Bin [2 ]
Li, Keshen [1 ,2 ]
机构
[1] Guangdong Med Coll, Inst Neurol, Zhanjiang 524001, Peoples R China
[2] Guangdong Med Coll, Affiliated Hosp, Guangdong Key Lab Age Related Cardiac & Cerebral, Zhanjiang 524001, Peoples R China
[3] Harbin Med Univ, Affiliated Hosp 4, Dept Neurosurg, Harbin, Peoples R China
来源
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2015年 / 11卷 / 02期
关键词
glioma; PAK5; tumor development; RNA interference; cell cycle arrest; P21-ACTIVATED KINASE-5; HUMAN-BRAIN; GENE; MITOCHONDRIA; EXPRESSION; CANCER;
D O I
10.7150/ijbs.9193
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glioma is the most common type of primary intracranial tumor and is highly lethal due to its pathogenetic location, high invasiveness, and poor prognosis. Even combined surgery and chemoradiotherapy do not effectively rescue glioma patients. Molecular target therapy is considered a safe and promising therapy for glioma. The identification of a novel, effective target protein in gliomas is of great interest. We found that PAK5 was highly expressed in the tumor tissues of glioma patients and human glioma cell lines. We then used a lentivirus-delivered short hairpin RNA to stably silence PAK5 expression in glioma cells and explore its influence. The results showed that the inhibition of PAK5 reduced cell viability and delayed the cell cycle at the G0/G1 phase in the glioma cells with PAK5 high expression. In addition, silencing PAK5 expression in U87 cells weakened their colony formation ability and in vivo tumorigenesis ability. Further studies demonstrated that PAK5 inhibition led to an increase in cleaved caspase 3 and a decrease in beta-catenin. In conclusion, our results suggest that the inhibition of PAK5 by RNA interference might efficiently suppress tumor development of glioma cells with PAK5 high expression. This finding provides a novel, promising therapeutic target for glioma treatment.
引用
收藏
页码:230 / 237
页数:8
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