EZH2 (enhancer of zeste homolog 2) is an important component of the Polycomb Repressive Complex 2 (PRC2) and is essential for the epigenetic regulation of gene expression. EZH2 primarily methylates histone H3 at lysine 27 (H3K27me3) to repress target gene transcription, particularly concerning tumor suppressor genes. The silencing of these genes ultimately promotes cancer by facilitating several important processes, a notable one being epithelial-mesenchymal transition (EMT), which promotes the invasiveness and metastatic potential of cancer cells, particularly in digestive system cancers. In addition to its role in histone modification, EZH2 interacts with diverse noncoding RNA species, including long noncoding RNAs (lncRNAs) and microRNAs, which can influence expression and activity. These interactions form elaborate regulatory pathways through which EZH2 enhances its oncogenic abilities. For example, lncRNAs recruit EZH2 to specific gene promoters and promote EZH2's repressive function to repress important tumor suppressor genes seen in colon, gastric, and esophageal cancers. Also, EZH2 overexpression has been associated with poor prognosis in several cancers, including gastrointestinal cancers. EZH2 overexpression is linked with aggressive tumor behavior and contributes to therapeutic resistance as cancer cells adapt to avoid the effects of traditional cancer therapy. EZH2 allows cancer cells to persist and proliferate in response to therapy by silencing genes that control apoptosis and the cell cycle. Since EZH2 is strongly associated with poor prognosis and therapeutic resistance in digestive cancers, targeting EZH2 will be a highly effective therapeutic strategy. This in-depth review suggests that further efforts will be required to thoroughly characterize the complex molecular networks that involve EZH2, especially with the hope of generating new therapeutic pathways in malignant cancers of the digestive system.

Keywords: Cancer; Colorectal; EZH2; Esophageal; Gastric; LncRNA.

Copyright © 2025. Published by Elsevier Inc.

增强子zeste同源物2（EZH2）是Polycomb抑制复合体2（PRC2）的重要组成部分，对于基因表达的表观遗传调控至关重要。EZH2主要在组蛋白H3赖氨酸27处进行甲基化（H3K27me3），以抑制靶基因转录，特别是与肿瘤抑制基因相关。这些基因沉默最终通过促进包括上皮-间充质转化（EMT）在内的多种重要过程来促进癌症发展，这增强了癌细胞的侵袭性和转移潜能，尤其是在消化系统癌症中。除了在组蛋白修饰中的作用外，EZH2还与其他非编码RNA种类相互作用，如长链非编码RNA（lncRNA）和microRNA，这些可以影响表达和活性。这些相互作用形成了复杂的调控途径，通过该途径EZH2增强了其致癌能力。例如，lncRNA将EZH2招募到特定基因启动子上，并促进EZH2的抑制功能以抑制结肠癌、胃癌和食道癌中的重要肿瘤抑制基因。此外，在包括消化系统癌症在内的多种癌症中，EZH2过表达与预后不良相关联。EZH2过表达与侵袭性肿瘤行为有关，并有助于产生治疗抵抗，因为癌细胞适应传统癌症疗法的影响以避免其效果。通过沉默控制凋亡和细胞周期的基因，EZH2使癌细胞能够对治疗作出反应并持续增殖。由于EZH2与消化系统癌症中的不良预后和治疗抵抗高度相关联，针对EZH2将是一种非常有效的治疗方法。这篇综述表明，为了彻底描述涉及EZH2的复杂分子网络（特别是在恶性消化系统癌症中生成新的治疗途径方面），需要进一步的努力。

关键词：癌症；结直肠癌；EZH2；食道癌；胃癌；lncRNA。

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