EZH2 promotes gastric cancer cells proliferation by repressing p21 expression

Pathol Res Pract. 2019 Jun;215(6):152374. doi: 10.1016/j.prp.2019.03.003. Epub 2019 Mar 4.

Abstract

EZH2 is a core component of the polycomb repressive complex 2 (PRC2), which catalyzes trimethylation of histone H3 lysine 27 (H3K27me3) and promotes carcinogenesis by epigenetically silencing many tumor suppressor genes. Increased EZH2 expression is a marker of advanced and metastatic in many cancers, including lung, prostate and breast cancer, and it has been considered as a potential novel therapeutic target. However, the clinical significance and molecular mechanisms of EZH2 controlling gastric cancer cell proliferation and invasion are not well documented. In this study, immunohistochemical analysis was conducted to investigate the EZH2 expression in gastric cancer. We found that EZH2 levels were increased in gastric cancer tissues compared with adjacent normal tissues. Moreover, patients with high levels of EZH2 expression had a relatively poor prognosis. Furthermore, knockdown of EZH2 expression by siRNA could impair cell proliferation and invasion both in vitro and vivo. Finally, we found that EZH2 influences gastric cancer cells proliferation partly through regulating p21 expression. Our findings present that EZH2 over-expression can be identified as a poor prognostic biomarker in gastric cancer.

Keywords: EZH2; Gastric cancer; Poor prognosis; Proliferation; p21.

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein