Zhou Xuan, Ren Yu, Zhang Jing, Zhang Chuanbao, Zhang Kailiang, Han Lei, Kong Lingping, Wei Jianwei, Chen Luyue, Yang Jingxuan, Wang Qixue, Zhang Jianning, Yang Yuqi, Jiang Tao, Li Min, Kang Chunsheng
Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin 300052, China.
The Department of Otorhinolaryngology and Maxillofacial Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin 300060, China.
Oncotarget. 2015 Apr 10;6(10):8353-65. doi: 10.18632/oncotarget.3229.
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.
HOTAIR是一种负性预后因子，在包括多形性胶质母细胞瘤（GBM）在内的多种人类癌症中均有过表达。对中国胶质瘤基因组图谱（CGGA）患者数据的生存分析表明，HOTAIR高表达与GBM患者的不良预后相关。NLK（Nemo样激酶）是β-连环蛋白通路的负调节因子，与HOTAIR表达呈负相关。当β-连环蛋白通路被抑制时，GBM细胞易发生细胞周期阻滞并抑制侵袭。在人胶质瘤来源的星形细胞瘤中导入HOTAIR 5'结构域可诱导β-连环蛋白。使用颅内动物模型证实，HOTAIR缺失可抑制GBM细胞迁移/侵袭。在原位模型中，体内GBM形成需要HOTAIR。总之，HOTAIR是GBM中一个潜在的治疗靶点。
