The atypical protein kinase RIOK3 contributes to glioma cell proliferation/survival, migration/invasion and the AKT/mTOR signaling pathway
The atypical protein kinase RIOK3 contributes to glioma cell proliferation/survival, migration/invasion and the AKT/mTOR signaling pathway
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非典型蛋白激酶 RIOK3 有助于神经胶质瘤细胞增殖/存活、迁移/侵袭以及 AKT/mTOR 信号通路
DOI：
10.1016/j.canlet.2017.12.010
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发表时间：
2018-02-28
期刊：
影响因子：
9.7
通讯作者：
Gao, Shangfeng
中科院分区：
文献类型：
--
作者：
Zhang, Tong;Ji, Daofei;Gao, Shangfeng
RIO（右开放阅读框）蛋白激酶包括RIOK 1、RIOK 2和RIOK 3。新出现的证据表明RIO激酶在癌细胞增殖、凋亡、迁移和侵袭中起重要作用。然而，RIOK 3在胶质瘤进展过程中的表达谱和具体作用在很大程度上是未知的。在目前的研究中，定量实时PCR，Western blot和免疫组化分析表明，RIOK 3在胶质瘤组织中上调。现有的数据库分析显示，较高水平的RIOK 3与胶质瘤患者较差的生存结局相关。流式细胞术、CCK 8和EdU检测显示RIOK 3的下调可阻滞细胞周期进程并抑制胶质瘤细胞增殖。创伤愈合、transwell和明胶酶谱分析显示沉默RIOK 3降低胶质瘤细胞迁移和侵袭。此外，RIOK 3的下调显著降低了胶质瘤细胞中AKT/mTOR信号转导的活性，并诱导了胶质瘤细胞的凋亡。RIOK 3的过表达对胶质瘤细胞增殖、迁移、侵袭和AKT/mTOR通路表现出相反的作用。这些结果表明，神经胶质瘤中的高RIOK 3水平似乎有助于这种癌症的生长和扩展，因此可以作为一种新的治疗靶点。(C)2017爱思唯尔B. V.保留所有权利。
The RIO (right open reading frame) protein kinases include RIOK1, RIOK2 and RIOK3. Emerging evidence has suggested an important role of RIO kinases in cancer cell proliferation, apoptosis, migration and invasion. However, the expression profile and specific roles of RIOK3 are largely unknown during glioma progression. In the current study, quantitative real-time PCR, Western blot, and immunohistochemical analysis showed that RIOK3 was upregulated in glioma tissues. Available database analysis revealed that higher levels of RIOK3 were associated with poorer survival outcome in glioma patients. Flow cytometry, CCK8 and EdU assays showed that downregulation of RIOK3 arrested cell cycle progression and inhibited glioma cell proliferation. Wound healing, transwell and gelatin zymography assays revealed that silencing RIOK3 decreased glioma cell migration and invasion. Furthermore, the downregulation of RIOK3 significantly decreased the activity of AKT/mTOR signaling and induced apoptosis in glioma cells. Overexpression of RIOK3 showed the opposite effects on glioma cell proliferation, migration, invasion and the AKT/mTOR pathway. These results indicate that high RIOK3 levels in gliomas appear to contribute to the growth and expansion of this cancer, and may thus serve as a novel therapeutic target. (C) 2017 Elsevier B.V. All rights reserved.