Oncotarget

Research Papers:

HOTAIR is a therapeutic target in glioblastoma

Xuan Zhou _, Yu Ren, Jing Zhang, Chuanbao Zhang, Kailiang Zhang, Lei Han, Lingping Kong, Jianwei Wei, Luyue Chen, Jingxuan Yang, Qixue Wang, Jianning Zhang, Yuqi Yang, Tao Jiang, Min Li and Chunsheng Kang

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Oncotarget. 2015; 6:8353-8365. https://doi.org/10.18632/oncotarget.3229

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Abstract

Xuan Zhou1,2,*, Yu Ren3,*, Jing Zhang4,*, Chuanbao Zhang5,*, Kailiang Zhang1,6, Lei Han1, Lingping Kong2, Jianwei Wei1, Luyue Chen1, Jingxuan Yang6, Qixue Wang1, Jianning Zhang1, Yuqi Yang7, Tao Jiang5, Min Li2,6, Chunsheng Kang1

1Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin 300052, China

2The 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

3Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China

4Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China

5Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China

6Department of Medicine, Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104,USA

7Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China

*These authors have contributed equally to this work

Correspondence to:

Chunsheng Kang, e-mail: kang97061@gmail.com

Tao Jiang, e-mail: jiangtao369@sohu.com

Min Li, e-mail: Min-Li@ouhsc.edu

Keywords: HOTAIR, NLK (Nemo-like kinase), β-catenin, PRC2 (Polycomb repressive complex 2), Glioblastoma

Received: December 01, 2014     Accepted: January 28, 2015     Published: March 21, 2015

ABSTRACT

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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