Document Detail

Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98.
MedLine Citation:
PMID:  21368858     Owner:  NLM     Status:  MEDLINE    
There is increasing evidence supporting the role of members of the polycomb group (PcG) gene family in tumor development and progression. However, their precise role in tumorigenesis and mechanisms of their regulation remain to be elucidated. Using nasopharyngeal carcinoma (NPC) as a disease model, a comprehensive analysis was undertaken on the clinical significance of EZH2 expression, identification of the cellular processes regulated by EZH2, and the mechanisms of its deregulated expression. Herein, we report EZH2 as being associated with a higher risk of relapse in NPC patients (P = 0.002). Genome-wide microarray and bioinformatics identified several vital cellular processes (such as differentiation, development, and apoptosis) to be regulated by EZH2, corroborated by in vitro lethality, and delayed tumor formation in vivo upon EZH2 depletion. The combination of global microRNA (miR) profiling in primary NPC specimens, and in silico analyses provided several candidate miRs that could regulate EZH2. Using a luciferase-based assay, miR-26a, miR-101, and miR-98 were validated as bona fide regulators of EZH2 expression. In particular, miR-98 was underexpressed in relapsed patient samples, strongly suggesting an important role for the miR-98 and EZH2 axis in NPC biology.
N M Alajez; W Shi; A B Y Hui; J Bruce; M Lenarduzzi; E Ito; S Yue; B O'Sullivan; F-F Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-21
Journal Detail:
Title:  Cell death & disease     Volume:  1     ISSN:  2041-4889     ISO Abbreviation:  Cell Death Dis     Publication Date:  2010  
Date Detail:
Created Date:  2011-03-03     Completed Date:  2011-06-14     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101524092     Medline TA:  Cell Death Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  e85     Citation Subset:  IM    
Division of Applied Molecular Oncology, Ontario Cancer Institute, Toronto, Canada.
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MeSH Terms
3' Untranslated Regions
Carcinoma / metabolism*
Cell Differentiation
Cell Survival
Computational Biology
DNA-Binding Proteins / genetics,  metabolism*
MicroRNAs / metabolism*
Nasopharyngeal Neoplasms / metabolism
Oligonucleotide Array Sequence Analysis
Polycomb Repressive Complex 2
Transcription Factors / genetics,  metabolism*
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/3' Untranslated Regions; 0/DNA-Binding Proteins; 0/MIRN101 microRNA, human; 0/MIRN26A microRNA, human; 0/MIRN98 microRNA, human; 0/MicroRNAs; 0/Transcription Factors; EC protein, human; EC Repressive Complex 2

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