G9a, also named EHMT2, is a histone 3 lysine 9 (H3K9) methyltransferase responsible for catalyzing H3K9 mono- and dimethylation (H3K9me1 and H3K9me2). G9a contributes to various aspects of embryonic development and tissue differentiation through epigenetic regulation. Furthermore, the aberrant expression of G9a is frequently observed in various tumors, particularly in prostate cancer, where it contributes to cancer pathogenesis and progression. This review highlights the critical role of G9a in multiple cancer-related processes, such as epigenetic dysregulation, tumor suppressor gene silencing, cancer lineage plasticity, hypoxia adaption, and cancer progression. Despite the increased research on G9a in prostate cancer, there are still significant gaps, particularly in understanding its interactions within the tumor microenvironment and its broader epigenetic effects. Furthermore, this review discusses the recent advancements in G9a inhibitors, including the development of dual-target inhibitors that target G9a along with other epigenetic factors such as EZH2 and HDAC. It aims to bring together the existing knowledge, identify gaps in the current research, and suggest future directions for research and treatment strategies.
G9a（亦称EHMT2）是一种组蛋白H3第9位赖氨酸（H3K9）甲基转移酶，负责催化H3K9的单甲基化与二甲基化（H3K9me1与H3K9me2）。G9a通过表观遗传调控参与胚胎发育与组织分化的多个环节。此外，G9a的异常表达常见于多种肿瘤，尤其在前列腺癌中，它参与癌症的发生与发展进程。本综述重点阐述G9a在表观遗传失调、抑癌基因沉默、癌症谱系可塑性、低氧适应及癌症进展等多种肿瘤相关过程中的关键作用。尽管针对G9a在前列腺癌中的研究日益增多，目前仍存在显著认知空白，特别是在理解其与肿瘤微环境的相互作用及其更广泛的表观遗传效应方面。此外，本文还探讨了G9a抑制剂的最新进展，包括针对G9a与EZH2、HDAC等其他表观遗传因子的双靶点抑制剂的研发。本综述旨在整合现有研究成果，指出现有研究的不足，并为未来研究方向及治疗策略提供建议。
G9a in Cancer: Mechanisms, Therapeutic Advancements, and Clinical Implications
肿瘤(癌症)患者之家