EZH2是致癌基因，编码蛋白是多梳抑制复合物2（PRC2）的催化组分，它通过催化组蛋白H3赖氨酸27（H3K27）的二甲基化和三甲基化来负责转录抑制。EZH2需要PRC2复合物的其他成员来完全行使甲基转移酶活性，包括SUZ12和EDE，PRC2在抑制发育调控因子如Hox基因和在X失活中具有重要功能。此外，非编码RNA可以指导EZH2基因到基因组的靶点行使基因抑制功能。在淋巴瘤、膀胱癌、黑色素瘤、前列腺癌、肺癌、乳腺癌等多种恶性肿瘤中检测到EZH2过表达，并与晚期和不良预后有关。此外，EZH2的功能获得性突变常在滤泡性淋巴瘤和弥漫性大B细胞淋巴瘤中发生。EZH2也可作为某些肿瘤类型的抑癌基因，在骨髓增生异常综合征（MDS）和骨髓增生性肿瘤（MPN）中可经常观察到失活突变，由此可见，EZH2在多种类型癌症中起到的重要作用。

EZH2 is the catalytic component of the Polycomb repressive complex 2 (PRC2) which is responsible for transcriptional repression by catalyzing di- and tri-methylation of Histone H3 lysine 27 (H3K27). EZH2 requires other members of the PRC2 complex for full methyltransferase activity, including SUZ12 and EED, and PRC2 function is important in repression of developmental regulators such as the HOX genes, and X-inactivation. Additionally, non-coding RNA's can guide EZH2 to genomic targets for gene repression. EZH2 overexpression is found in many malignancies including lymphoma, bladder cancer, melanoma, prostate cancer, lung cancer, and breast cancer, and is associated with advanced stage and poor prognosis. Furthermore, gain-of-function mutations in EZH2 occur frequently in follicular lymphoma and diffuse large B-cell lymphomas. EZH2 can also act as a tumor suppressor in certain cancer types, and recurrent inactivating mutations are observed in myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). Given its importance in multiple cancer types, EZH2 inhibition has shown promise in pre-clinical studies and is a current effort in multiple clinical trials, either through direct inhibition of EZH2 enzymatic activity or through disruption in PRC2 stability.

GeneCards OncoKB My Cancer Genome