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Efficient inhibition of human glioma development by RNA interference-mediated silencing of PAK5.

Gu X, Wang C, Wang X, Ma G, Li Y, Cui L, Chen Y, Zhao B, Li K - Int. J. Biol. Sci. (2015)

Bottom Line: Even combined surgery and chemoradiotherapy do not effectively rescue glioma patients.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

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PAK5 is highly expressed in glioma cells. (A) The ratio of PAK5 mRNA expression in freshly sampled gliomas and their adjacent normal tissues from 40 glioma patients. (B) Representative immunohistochemical staining of PAK5 expression in human glioma tissues (upper) and pericancerous tissues (lower). (C) Western blot assay of PAK5 expression in glioma cell lines.
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Figure 1: PAK5 is highly expressed in glioma cells. (A) The ratio of PAK5 mRNA expression in freshly sampled gliomas and their adjacent normal tissues from 40 glioma patients. (B) Representative immunohistochemical staining of PAK5 expression in human glioma tissues (upper) and pericancerous tissues (lower). (C) Western blot assay of PAK5 expression in glioma cell lines.

Mentions: PAK5 expression levels in human gliomas have not been previously determined, and thus, we first detected PAK5 mRNA expression in freshly sampled gliomas and in matched pericancerous tissues from 40 glioma patients. The data suggested that PAK5 mRNA expression is markedly higher in cancerous tissue than in pericancerous tissue in most (35 to 40) glioma patients (Fig. 1A). To confirm the high expression of PAK5 in gliomas, we performed immunohistochemical analysis to evaluate PAK5 expression in human gliomas. The glioma tissue exhibited strong positive staining by the anti-PAK5 antibody, whereas PAK5 expression levels were low in most pericancerous tissues of glioma patients (Fig. 1B). However, PAK5 expression had no obvious correlations with grades of glioma tumors (Table 1). On the other hand, immunoblot analysis demonstrated that PAK5 expression levels are high in human glioma cell lines, particularly in U87 and SHG44 cells (Fig. 1C). Taken together, these data suggest that PAK5 expression is upregulated in human gliomas.


Efficient inhibition of human glioma development by RNA interference-mediated silencing of PAK5.

Gu X, Wang C, Wang X, Ma G, Li Y, Cui L, Chen Y, Zhao B, Li K - Int. J. Biol. Sci. (2015)

PAK5 is highly expressed in glioma cells. (A) The ratio of PAK5 mRNA expression in freshly sampled gliomas and their adjacent normal tissues from 40 glioma patients. (B) Representative immunohistochemical staining of PAK5 expression in human glioma tissues (upper) and pericancerous tissues (lower). (C) Western blot assay of PAK5 expression in glioma cell lines.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4308408&req=5

Figure 1: PAK5 is highly expressed in glioma cells. (A) The ratio of PAK5 mRNA expression in freshly sampled gliomas and their adjacent normal tissues from 40 glioma patients. (B) Representative immunohistochemical staining of PAK5 expression in human glioma tissues (upper) and pericancerous tissues (lower). (C) Western blot assay of PAK5 expression in glioma cell lines.
Mentions: PAK5 expression levels in human gliomas have not been previously determined, and thus, we first detected PAK5 mRNA expression in freshly sampled gliomas and in matched pericancerous tissues from 40 glioma patients. The data suggested that PAK5 mRNA expression is markedly higher in cancerous tissue than in pericancerous tissue in most (35 to 40) glioma patients (Fig. 1A). To confirm the high expression of PAK5 in gliomas, we performed immunohistochemical analysis to evaluate PAK5 expression in human gliomas. The glioma tissue exhibited strong positive staining by the anti-PAK5 antibody, whereas PAK5 expression levels were low in most pericancerous tissues of glioma patients (Fig. 1B). However, PAK5 expression had no obvious correlations with grades of glioma tumors (Table 1). On the other hand, immunoblot analysis demonstrated that PAK5 expression levels are high in human glioma cell lines, particularly in U87 and SHG44 cells (Fig. 1C). Taken together, these data suggest that PAK5 expression is upregulated in human gliomas.

Bottom Line: Even combined surgery and chemoradiotherapy do not effectively rescue glioma patients.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

Show MeSH
Related in: MedlinePlus