ARHGDIA的下调通过激活Rho GTPase信号通路促进人类胶质瘤进展。
Downregulation of ARHGDIA contributes to human glioma progression through activation of Rho GTPase signaling pathway.
作者信息
Lu Weiliang, Wang Xixi, Liu Jingjing, He Yu, Liang Ziwei, Xia Zijing, Cai Ying, Zhou Liangxue, Zhu Hongxia, Liang Shufang
机构信息
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No.17, 3rd Section of People's South Road, Chengdu, 610041, Republic of China.
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, Republic of China.
出版信息
Tumour Biol. 2016 Dec;37(12):15783–15793. doi: 10.1007/s13277-016-5374-6. Epub 2016 Oct 10.
The protein ARHGDIA has been found to play distinct roles in cancer progression for several tumors. However, it remains elusive whether and how ARHGDIA plays functions in human glioma. In this study, we discovered that ARHGDIA is much downregulated in human glioma; meanwhile, its expression negatively correlates with glioma malignancy and positively relates to prognosis of glioma patients. It has independent predictive value of ARHGDIA expression level for overall survival of human glioma patients. Glioma patients with ARHGDIA-positive expression have a longer overall survival time than ARHGDIA-negative patients. Knockdown of ARHGDIA promotes cell proliferation, cell cycle progression, and cell migration due to the activation of Rho GTPases (Rac1, Cdc42, and RhoA) and Akt phosphorylation, whereas overexpression of ARHGDIA suppresses cell growth, cell cycle progression, and cell migration. ARHGDIA is a potential prognostic marker and therapeutic target for human glioma.
已发现蛋白质ARHGDIA在多种肿瘤的癌症进展中发挥不同作用。然而，ARHGDIA是否以及如何在人类胶质瘤中发挥作用仍不清楚。在本研究中，我们发现ARHGDIA在人类胶质瘤中表达显著下调；同时，其表达与胶质瘤恶性程度呈负相关，与胶质瘤患者的预后呈正相关。ARHGDIA表达水平对人类胶质瘤患者的总生存期具有独立的预测价值。ARHGDIA阳性表达的胶质瘤患者总生存时间比ARHGDIA阴性患者长。敲低ARHGDIA会由于Rho GTPases（Rac1、Cdc42和RhoA）的激活和Akt磷酸化而促进细胞增殖、细胞周期进程和细胞迁移，而ARHGDIA的过表达则抑制细胞生长、细胞周期进程和细胞迁移。ARHGDIA是人类胶质瘤潜在的预后标志物和治疗靶点。
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