Efficient inhibition of human glioma development by RNA interference-mediated silencing of PAK5.
Efficient inhibition of human glioma development by RNA interference-mediated silencing of PAK5.
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通过 RNA 干扰介导的 PAK5 沉默有效抑制人神经胶质瘤的发展。
DOI：
10.7150/ijbs.9193
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发表时间：
2015
影响因子：
9.2
通讯作者：
Li K
中科院分区：
文献类型：
--
作者：
Gu X;Wang C;Wang X;Ma G;Li Y;Cui L;Chen Y;Zhao B;Li K
胶质瘤是最常见的原发性颅内肿瘤，因其发病部位、侵袭性高、预后差而致死率较高。即使联合手术和放化疗也不能有效挽救神经胶质瘤患者。分子靶向治疗被认为是一种安全且有前途的神经胶质瘤治疗方法。神经胶质瘤中一种新型、有效的靶蛋白的鉴定引起了人们的极大兴趣。我们发现PAK5在神经胶质瘤患者的肿瘤组织和人神经胶质瘤细胞系中高表达。然后，我们使用慢病毒传递的短发夹 RNA 来稳定沉默胶质瘤细胞中的 PAK5 表达并探索其影响。结果表明，在PAK5高表达的胶质瘤细胞中，抑制PAK5可降低细胞活力，并使细胞周期延迟至G0/G1期。此外，沉默U87细胞中PAK5的表达会削弱其集落形成能力和体内致瘤能力。进一步的研究表明，PAK5 抑制导致裂解的 caspase 3 增加和 β-连环蛋白减少。总之，我们的结果表明，通过RNA干扰抑制PAK5可以有效抑制PAK5高表达的神经胶质瘤细胞的肿瘤发展。这一发现为神经胶质瘤的治疗提供了一个新颖、有前景的治疗靶点。
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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影响因子：
4
作者：
Wu, Xiaochong;Carr, Heather S.;Dan, Ippeita;Ruvolo, Peter P.;Frost, Jeffrey A.
通讯作者：
Frost, Jeffrey A.
影响因子：
5.3
作者：
Li, XF;Minden, A
通讯作者：
Minden, A
影响因子：
--
作者：
Wang, Xia;Gong, Wei;Jiang, Bo
通讯作者：
Jiang, Bo
影响因子：
3.3
作者：
Han, Zheng-Xiang;Wang, Xiao-Xia;Zheng, Jun-Nian
通讯作者：
Zheng, Jun-Nian
影响因子：
5.3
作者：
Dan, C;Nath, N;Minden, A
通讯作者：
Minden, A