G9a in Cancer: Mechanisms, Therapeutic Advancements, and Clinical Implications.

Simple Summary: In this review, we have summarized the crucial role of G9a in cellular biology and disease. By synthesizing recent research discoveries, we delve into the functions of G9a in gene expression regulation, cell proliferation, and biological development. Additionally, we explore its potential involvement in cancer and discuss its prospects as a therapeutic target specifically in prostate cancer. In summary, this review provides a comprehensive perspective on G9a, enhances understanding of the significance of G9a in biology and cancer, and offers insights into future research and drug development. 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. [ABSTRACT FROM AUTHOR]