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Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner.
MedLine Citation:
PMID:  25428914     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Kailiang Zhang; Xiaotian Sun; Xuan Zhou; Lei Han; Luyue Chen; Zhendong Shi; Anling Zhang; Minhua Ye; Qixue Wang; Chaoyong Liu; Jianwei Wei; Yu Ren; Jingxuan Yang; Jianning Zhang; Peiyu Pu; Min Li; Chunsheng Kang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-4
Journal Detail:
Title:  Oncotarget     Volume:  -     ISSN:  1949-2553     ISO Abbreviation:  Oncotarget     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-27     Completed Date:  -     Revised Date:  2014-11-28    
Medline Journal Info:
Nlm Unique ID:  101532965     Medline TA:  Oncotarget     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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