EZH2: An Accomplice of Gastric Cancer

Simple Summary Enhancer of zeste homolog 2 (EZH2) modifies the trimethylation of Lys-27 of histone 3, affecting downstream target genes' expression. It was reported that EZH2 is highly expressed in gastric cancer and may be a potential prognostic molecule and promising therapeutic target. We aim to present the value of EZH2 research in gastric cancer by focusing on the crucial events of EZH2 involvement in gastric cancer progression. Therefore, in this review, we present the two main functions of EZH2: histone methylation modification and DNA methylation by EZH2; the molecular mechanism of the action of EZH2 in regulating target genes; a detailed description of the mechanism of EZH2 in gastric cancer-related events. Finally, progress in the development of EZH2 inhibitors is summarized. This review article provides researchers studying the epigenetics of gastric cancer with research ideas to find new targets for studying gastric cancer pathogenesis. Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Understanding the factors influencing the therapeutic effects in gastric cancer patients and the molecular mechanism behind gastric cancer is still facing challenges. In addition to genetic alterations and environmental factors, it has been demonstrated that epigenetic mechanisms can also induce the occurrence and progression of gastric cancer. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressor complex 2 (PRC2), which trimethylates histone 3 at Lys-27 and regulates the expression of downstream target genes through epigenetic mechanisms. It has been found that EZH2 is overexpressed in the stomach, which promotes the progression of gastric cancer through multiple pathways. In addition, targeted inhibition of EZH2 expression can effectively delay the progression of gastric cancer and improve its resistance to chemotherapeutic agents. Given the many effects of EZH2 in gastric cancer, there are no studies to comprehensively describe this mechanism. Therefore, in this review, we first introduce EZH2 and clarify the mechanisms of abnormal expression of EZH2 in cancer. Secondly, we summarize the role of EZH2 in gastric cancer, which includes the association of the EZH2 gene with genetic susceptibility to GC, the correlation of the EZH2 gene with gastric carcinogenesis and invasive metastasis, the resistance to chemotherapeutic drugs of gastric cancer mediated by EZH2 and the high expression of EZH2 leading to poor prognosis of gastric cancer patients. Finally, we also clarify some of the current statuses of drug development regarding targeted inhibition of EZH2/PRC2 activity.