title: Efficient inhibition of human glioma development by RNA interference-mediated silencing of PAK5.
abstract: 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 β-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.
authors: 1. Institute of Neurology, Guangdong Medical College, Zhanjiang, China. ; 2. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors: Xuefeng
authors: X
authors: Gu
authors: 3. Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Ce
authors: C
authors: Wang
authors: 3. Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Xuefeng
authors: X
authors: Wang
authors: 1. Institute of Neurology, Guangdong Medical College, Zhanjiang, China.
authors: Guoda
authors: G
authors: Ma
authors: 2. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors: You
authors: Y
authors: Li
authors: 1. Institute of Neurology, Guangdong Medical College, Zhanjiang, China.
authors: Lili
authors: L
authors: Cui
authors: 2. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors: Yanyan
authors: Y
authors: Chen
authors: 2. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors: Bin
authors: B
authors: Zhao
authors: 1. Institute of Neurology, Guangdong Medical College, Zhanjiang, China. ; 2. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors: Keshen
authors: K
authors: Li
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D006801:Humans; D034622:RNA Interference / Q000502:physiology*; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C443802:PAK5 protein, human; D054462:p21-Activated Kinases
keywords: PAK5; RNA interference; cell cycle arrest; glioma; tumor development
references: J Neurooncol. 2004 Jun;68(2):113-21
references: 15218947
references: Nature. 1985 Jan 10-18;313(5998):144-7
references: 2981413
references: Cancer Res. 1992 Jun 1;52(11):3213-9
references: 1317261
references: Science. 1997 Mar 28;275(5308):1943-7
references: 9072974
references: Trends Biochem Sci. 1999 Sep;24(9):350-5
references: 10470034
references: Mol Cell Biol. 2006 Apr;26(8):3215-30
references: 16581795
references: Cancer. 2007 Jul 1;110(1):13-24
references: 17520692
references: Biol Cell. 2008 Feb;100(2):97-108
references: 18199048
references: N Engl J Med. 2008 Jul 31;359(5):492-507
references: 18669428
references: J Cell Biochem. 2008 Sep 1;105(1):167-75
references: 18465753
references: Int J Cancer. 2009 Aug 1;125(3):548-55
references: 19415746
references: Tumour Biol. 2010 Dec;31(6):575-82
references: 20567954
references: Ann Neurol. 2011 Jul;70(1):9-21
references: 21786296
references: Cell. 2012 Jun 8;149(6):1192-205
references: 22682243
references: Brain Tumor Pathol. 2014 Oct;31(4):234-41
references: 24062079
references: Mol Cell Biol. 2002 Jan;22(2):567-77
references: 11756552
references: Mol Cell Biol. 2003 Aug;23(16):5526-39
references: 12897128
references: Mol Cell Biol. 2003 Oct;23(20):7134-42
references: 14517284