Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner
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Kailiang Zhang1,2,*, Xiaotian Sun2,3,*, Xuan Zhou4, Lei Han1, Luyue Chen1, Zhendong Shi1, Anling Zhang1, Minhua Ye5, Qixue Wang1, Chaoyong Liu6, Jianwei Wei1, Yu Ren7, Jingxuan Yang2, Jianning Zhang1, Peiyu Pu1, Min Li2 and Chunsheng Kang1
1 Department of Neurosurgery, Tianjin Medical University General Hospital; Laboratory of Neuro-Oncology, Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China
2 Department of Medicine, Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
3 Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
4 The Department of Otorhinolaryngology and Maxillofacial Oncology, Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute; National Clinical Research Center of Cancer, Tianjin, China
5 Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
6 School of Materials Science and Engineering, Tianjin University, Tianjin, China
7 Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China
* These authors contributed equally to this work
Min Li, email:
Chunsheng Kang, email:
Keywords: Long non-coding RNA; HOTAIR; GBM; Cell cycle; EZH2
Received: August 27, 2014 Accepted: November 04, 2014 Published: November 04, 2014
The long non-coding RNA Hox transcript antisense intergenic RNA (HOTAIR) was recently implicated in breast cancer metastasis and is predictive of poor prognosis in colorectal and pancreatic cancers. We recently discovered that HOTAIR is a cell cycle-related lncRNA in human glioma, and its expression is closely associated with glioma staging and poor prognosis. Although lysine specific demethylase 1 (LSD1) and polycomb repressive complex 2 (PRC2) have been demonstrated to be functional targets of HOTAIR, how HOTAIR regulates glioma cell cycle progression remains largely unknown. In this study, we found that EZH2 (predominant PRC2 complex component) inhibition blocked cell cycle progression in glioma cells, consistent with the effects elicited by HOTAIR siRNA. However, the inhibition of LSD1 did not affect cell cycle progression in glioma cells. These results suggest that HOTAIR might regulate cell cycle progression through EZH2. Our intracranial mice model also revealed delayed tumor growth in HOTAIR siRNA- and EZH2 inhibitor-treated groups. Moreover, in HOTAIR knock-down cell lines, the expression of the PRC2-binding domain of HOTAIR (5’ domain) but not of the LSD1-binding domain of HOTAIR (3’ domain) resulted in accelerated cell cycle progression. In conclusion, HOTAIR promotes cell cycle progression in glioma as a result of the binding of its 5’ domain to the PRC2 complex.
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