Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer.
Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer.
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DOI：
10.18632/oncotarget.16316
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发表时间：
2017-06-20
期刊：
影响因子：
--
通讯作者：
Fujii T
中科院分区：
文献类型：
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作者：
Oki S;Sone K;Oda K;Hamamoto R;Ikemura M;Maeda D;Takeuchi M;Tanikawa M;Mori-Uchino M;Nagasaka K;Miyasaka A;Kashiyama T;Ikeda Y;Arimoto T;Kuramoto H;Wada-Hiraike O;Kawana K;Fukayama M;Osuga Y;Fujii T
组蛋白甲基转移酶EZH 2是一种关键的表观遗传修饰剂，已知与人类肿瘤发生相关。然而，EZH 2的生理重要性及其在子宫内膜癌中的临床相关性仍不清楚。因此，在本研究中，我们研究EZH 2在子宫内膜癌中的表达和功能。在11个子宫内膜癌细胞系和52个临床子宫内膜癌标本的定量实时PCR分析中，与相应的正常对照细胞和组织相比，EZH 2在癌细胞和组织中显著过表达。使用TCGA RNA-seq数据库和组织微阵列（TMA）的数据进行的Kaplan-Meier生存分析表明，EZH 2过表达与子宫内膜癌预后相关。此外，使用特异性siRNA敲低EZH 2导致子宫内膜癌细胞的生长抑制和凋亡诱导，伴随着H3 K27三甲基化的减弱。与这些结果一致，用GSK 126（一种特异性EZH 2抑制剂）治疗抑制子宫内膜癌细胞生长并减少癌细胞集落的数量。此外，GSK 126显示与阿霉素或顺铂的累加效应，阿霉素或顺铂是治疗子宫内膜癌的常规药物。进一步的研究应该探索抑制EZH 2在子宫内膜癌患者中的治疗潜力。
The histone methyltransferase EZH2, a key epigenetic modifier, is known to be associated with human tumorigenesis. However, the physiological importance of EZH2 and its clinical relevance in endometrial cancer remain unclear. Hence, in the present study, we investigated the expression and function of EZH2 in endometrial cancer. In a quantitative real-time PCR analysis of 11 endometrial cancer cell lines and 52 clinical endometrial cancer specimens, EZH2 was significantly overexpressed in cancer cells and tissues compared to that in corresponding normal control cells and tissues. Kaplan-Meier survival analysis using data of the TCGA RNA-seq database and tissue microarrays (TMAs) indicated that EZH2 overexpression is associated with endometrial cancer prognosis. In addition, knockdown of EZH2 using specific siRNAs resulted in growth suppression and apoptosis induction of endometrial cancer cells, accompanied by attenuation of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased the number of cancer cell colonies. Furthermore, GSK126 showed additive effects with doxorubicin or cisplatin, which are conventional drugs for treatment of endometrial cancer. Further studies should explore the therapeutic potential of inhibiting EZH2 in patients with endometrial cancer.