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The RNA helicase DHX33 is required for cancer cell proliferation in human glioblastoma and confers resistance to PI3K/mTOR inhibition
Cellular Signalling ( IF 4.8 ) Pub Date : 2018-12-12 , DOI: 10.1016/j.cellsig.2018.12.005
Hongzhong Wang , Junyan Yu , Xingshun Wang , Yandong Zhang

Human Glioblastoma is one deadly disease; the median survival time is reported to be 13.9 months after treatment. In the present study, we discovered that DHX33 is highly expressed in 84% of all Glioblastoma multiforme (GBM). Knockdown of DHX33 led to significant reduced proliferation and migration in glioblastoma cells in vitro and in vivo. Mechanistically, DHX33 regulated a set of critical genes involved in cell cycle and cell migration to promote glioblastoma development. Additionally, DHX33 was found to be induced by inhibitors of PI3K and mTOR whose activation has been detected in 50% of glioblastoma. Overexpression of wild type DHX33 protein, but not the helicase dead mutant, confers resistance to mTOR inhibitors in glioblastoma cells. DHX33 probably functions as a critical regulator to promote GBM development. Our results highlight its therapeutic potential in treating GBM.



中文翻译:

RNA解旋酶DHX33是人胶质母细胞瘤中癌细胞增殖所必需的,并赋予对PI3K / mTOR抑制的抗性

人胶质母细胞瘤是一种致命的疾病。据报道中位生存时间为治疗后13.9个月。在本研究中,我们发现DHX33在所有多形胶质母细胞瘤(GBM)中84%高表达。敲低DHX33导致胶质母细胞瘤细胞体外体内增殖和迁移明显减少。从机制上讲,DHX33调节了一组与细胞周期和细胞迁移有关的关键基因,以促进胶质母细胞瘤的发展。此外,发现DHX33被PI3K和mTOR抑制剂诱导,其抑制剂已在50%的胶质母细胞瘤中被检测到。野生型DHX33蛋白的过表达,而不是解旋酶死亡的突变体,在成胶质细胞瘤细胞中赋予了对mTOR抑制剂的抗性。DHX33可能是促进GBM发展的关键调节剂。我们的结果突出了其在治疗GBM中的治疗潜力。

更新日期:2018-12-12
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