Targeting EZH2 regulates the biological characteristics of glioma stem cells via the Notch1 pathway

Exp Brain Res. 2023 Oct;241(10):2409-2418. doi: 10.1007/s00221-023-06693-8. Epub 2023 Aug 29.

Abstract

Glioma is the most common malignant brain tumor, and its behavior is closely related to the presence of glioma stem cells (GSCs). We found that the enhancer of zeste homolog 2 (EZH2) is highly expressed in glioma and that its expression is correlated with the prognosis of glioblastoma multiforme (GBM) in two databases: The Cancer Genome Atlas and the Chinese Glioma Genome Atlas. Additionally, EZH2 is known to regulate the stemness-associated gene expression, proliferation, and invasion ability of GSCs, which may be achieved through the activation of the STAT3 and Notch1 pathways. Furthermore, we demonstrated the effect of the EZH2-specific inhibitor GSK126 on GSCs; these results not only corroborate our hypothesis, but also provide a potential novel treatment approach for glioma.

Keywords: EZH2; GSK126; Glioma stem cells; Notch1; STAT3.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Asian People
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / metabolism
  • Enhancer of Zeste Homolog 2 Protein* / antagonists & inhibitors
  • Enhancer of Zeste Homolog 2 Protein* / genetics
  • Glioma* / drug therapy
  • Glioma* / genetics
  • Glioma* / metabolism
  • Humans
  • Neoplastic Stem Cells* / drug effects
  • Neoplastic Stem Cells* / metabolism

Substances

  • Antineoplastic Agents
  • Enhancer of Zeste Homolog 2 Protein
  • EZH2 protein, human
  • GSK-2816126
  • NOTCH1 protein, human
  • STAT3 protein, human