HOTAIR is a therapeutic target in glioblastoma.

HOTAIR is a therapeutic target in glioblastoma.
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Hotair是胶质母细胞瘤的治疗靶标。

DOI:
10.18632/oncotarget.3229
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发表时间:
2015-04-10
期刊:
影响因子:
--
通讯作者:
Kang C
Kang C
中科院分区:
其他
文献类型:
--
作者:
Zhou X;Ren Y;Zhang J;Zhang C;Zhang K;Han L;Kong L;Wei J;Chen L;Yang J;Wang Q;Zhang J;Yang Y;Jiang T;Li M;Kang C

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HOTAIR是一种负向预后因子,在包括多形性胶质母细胞瘤(GBM)在内的多种人类肿瘤中过度表达。中国人脑胶质瘤基因组图谱(CGGA)患者资料的生存分析表明,在GBM患者中HOTAIR高表达与预后不良相关。β-连环蛋白途径的负调控蛋白NLK与HOTAIR的表达呈负相关。当β-连环蛋白途径被抑制时,基底膜细胞对细胞周期停滞和侵袭抑制变得敏感。HOTAIR5‘结构域在人脑胶质瘤星形细胞瘤诱导的β-连环蛋白中的引入用颅内动物模型证实HOTAIR缺失抑制了GBM细胞的迁移/侵袭。在原位模型中,体内GBM的形成需要HOTAIR。综上所述,HOTAIR是治疗GBM的潜在靶点。
HOTAIR is a negative prognostic factor and is overexpressed in multiple human cancers including glioblastoma multiform (GBM). Survival analysis of Chinese Glioma Genome Atlas (CGGA) patient data indicated that high HOTAIR expression was associated with poor outcome in GBM patients. NLK (Nemo-like kinase), a negative regulator of the β-catenin pathway, was negatively correlated with HOTAIR expression. When the β-catenin pathway was inhibited, GBM cells became susceptible to cell cycle arrest and inhibition of invasion. Introduction of the HOTAIR 5′ domain in human glioma-derived astrocytoma induced β-catenin. An intracranial animal model was used to confirm that HOTAIR depletion inhibited GBM cell migration/invasion. In the orthotopic model, HOTAIR was required for GBM formation in vivo. In summary, HOTAIR is a potential therapeutic target in GBM.
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