title: Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner.
abstract: 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.
authors.affiliation: 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. Department of Medicine, Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Kailiang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Luyue
authors.initials: L
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Anling
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Ye
authors.affiliation: 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.
authors.forename: Qixue
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Materials Science and Engineering, Tianjin University, Tianjin, China.
authors.forename: Chaoyong
authors.initials: C
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wei
authors.affiliation: Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Medicine, Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.affiliation: Department of Medicine, Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D014162:Transfection
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2