Enhancer of Zeste Homolog 2 (EZH2) is a key epigenetic regulator known for its role in global gene silencing and is involved in a variety of cellular processes, including cell survival, proliferation, invasion, and self-renewal. As a core component of the Polycomb Repressive Complex 2 (PRC2), EZH2 catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3), leading to chromatin compaction and transcriptional repression. Dysregulated EZH2 expression is observed in a wide range of solid tumors and hematological malignancies and is frequently associated with increased metastatic potential and poor clinical outcomes. While EZH2 primarily mediates gene silencing through its canonical PRC2-dependent activity, it also exerts oncogenic effects via non-canonical mechanisms. In its non-canonical role, EZH2 acts independently of PRC2, interacting with other signaling molecules as a transcriptional activator or co-activator, thereby promoting the activation of oncogenic pathways. Through both canonical and non-canonical mechanisms, EZH2 significantly contributes to tumor initiation and its subsequent progression. Given its critical role in oncogenesis and cancer progression, EZH2 is under investigation as a potential biomarker for cancer diagnosis and prognosis. This review provides a comprehensive overview of EZH2’s function and oncogenic roles across human cancers. Enhanced insight into EZH2’s complex regulatory network may facilitate the development of more effective strategies to manage EZH2-driven malignancies.
Zeste同源物2增强子（EZH2）是一种关键的表观遗传调控因子，以其在全局基因沉默中的作用而闻名，并参与多种细胞过程，包括细胞存活、增殖、侵袭和自我更新。作为多梳抑制复合物2（PRC2）的核心组分，EZH2催化组蛋白H3第27位赖氨酸的三甲基化（H3K27me3），导致染色质压缩和转录抑制。EZH2表达失调在多种实体瘤和血液系统恶性肿瘤中被观察到，且常与转移潜能增强及不良临床结局相关。尽管EZH2主要通过其经典的PRC2依赖性活性介导基因沉默，但它也通过非经典机制发挥致癌作用。在其非经典作用中，EZH2独立于PRC2发挥作用，作为转录激活因子或共激活因子与其他信号分子相互作用，从而促进致癌通路的激活。通过经典和非经典机制，EZH2显著促进肿瘤的发生及其后续进展。鉴于其在肿瘤发生和癌症进展中的关键作用，EZH2正被研究作为癌症诊断和预后的潜在生物标志物。本综述全面概述了EZH2在人类癌症中的功能和致癌作用。对EZH2复杂调控网络的深入理解可能有助于制定更有效的策略来管理EZH2驱动的恶性肿瘤。
肿瘤(癌症)患者之家