Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98.
Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98.
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DOI：
10.1038/cddis.2010.64
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发表时间：
2010-10-21
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
越来越多的证据支持多梳组（PcG）基因家族成员在肿瘤发生和进展中的作用。然而，它们在肿瘤发生中的确切作用及其调节机制仍有待阐明。以鼻咽癌（NPC）为模型，对EZH 2表达的临床意义、EZH 2调控的细胞过程及其失调控机制进行了综合分析。在此，我们报告EZH 2与NPC患者的较高复发风险相关（P=0.002）。全基因组微阵列和生物信息学鉴定了EZH 2调控的几个重要细胞过程（如分化、发育和凋亡），通过体外致死性和EZH 2耗尽后体内延迟的肿瘤形成来证实。原发性NPC标本中的全局microRNA（miR）谱分析和计算机模拟分析的组合提供了几种可以调节EZH 2的候选miR。使用基于酶的测定，miR-26 a、miR-101和miR-98被验证为EZH 2表达的真正调节剂。特别是，miR-98在复发患者样本中表达不足，强烈表明miR-98和EZH 2轴在NPC生物学中的重要作用。
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.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5
作者：
Hui, Angela B. Y.;Shi, Wei;Liu, Fei-Fei
通讯作者：
Liu, Fei-Fei
影响因子：
64.8
作者：
Varambally, S;Dhanasekaran, SM;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM
影响因子：
82.9
作者：
Piontek, Klaus;Menezes, Luis F.;Germino, Gregory G.
通讯作者：
Germino, Gregory G.
DOI：
10.1523/jneurosci.5303-08.2009
发表时间：
2009-01-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chatoo W;Abdouh M;David J;Champagne MP;Ferreira J;Rodier F;Bernier G
通讯作者：
Bernier G