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

Author:

Ni Yuchao123,Shi Mingchen23,Liu Liangliang23,Lin Dong23ORCID,Zeng Hao1,Ong Christopher23ORCID,Wang Yuzhuo234ORCID

Affiliation:

1. Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China

2. Vancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada

3. Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada

4. Department of Experimental Therapeutics, BC Cancer, Vancouver, BC V5Z 1L3, Canada

Abstract

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.

Funder

Canadian Institutes of Health Research

Terry Fox Research Institute

Canadian Cancer Society Breakthrough Team Grant generously supported by the Lotte & John Hecht Memorial Foundation

BC Cancer Foundation

the program of China Scholarships Council

Publisher

MDPI AG

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