Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98

被引:142
作者
Alajez, N. M. [1 ,2 ]
Shi, W. [1 ,2 ]
Hui, A. B. Y. [1 ,2 ]
Bruce, J. [1 ,2 ]
Lenarduzzi, M. [1 ,2 ]
Ito, E. [1 ,2 ]
Yue, S. [1 ]
O'Sullivan, B. [3 ,4 ]
Liu, F-F [1 ,2 ,3 ,4 ]
机构
[1] Ontario Canc Inst, Div Appl Mol Oncol, Toronto, ON M4X 1K9, Canada
[2] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada
[3] Univ Hlth Network, Dept Radiat Oncol, Toronto, ON, Canada
[4] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada
基金
加拿大健康研究院;
关键词
EZH2; microRNA; nasopharyngeal carcinoma (NPC); POLYCOMB REPRESSIVE COMPLEX; GROUP PROTEINS; BREAST-CANCER; CELLS; EXPRESSION; RADIATION; PATHWAY; GROWTH; VIRUS; GENES;
D O I
10.1038/cddis.2010.64
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. Cell Death and Disease (2010) 1, e85; doi: 10.1038/cddis.2010.64; published online 21 October 2010
引用
收藏
页码:e85 / e85
页数:10
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