EZH2: An Accomplice of Gastric Cancer

• Published in: Cancers Vol. 15; no. 2; p. 425
• Main Authors: Yu, Wuhan, Liu, Ning, Song, Xiaogang, Chen, Lang, Wang, Mancai, Xiao, Guohui, Li, Tengfei, Wang, Zheyuan, Zhang, Youcheng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.01.2023; MDPI
• Subjects: Carcinogenesis; Cell growth; Chemotherapy; DNA methylation; Drug development; Drug resistance; enhancer of zeste homolog 2; Environmental factors; Epigenetics; EZH2 gene; Gastric cancer; Gene expression; Genomes; H3K27; Histones; Metastases; Pathogenesis; Polycomb group proteins; Prostate cancer; Proteins; Review; RNA polymerase; Therapeutic targets; Tumorigenesis; H3K27; gastric cancer; enhancer of zeste homolog 2; epigenetics
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15020425

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.