EZH2 is a negative prognostic factor and exhibits pro-oncogenic activity in glioblastoma

Cancer Lett. 2015 Jan 28;356(2 Pt B):929-36. doi: 10.1016/j.canlet.2014.11.003. Epub 2014 Nov 11.

Abstract

The identification of single or less genes based on mRNA expression as clinical diagnostic markers for glioblastoma (GBM) remains a challenge. Recent data have shown the potential oncogenic role and prognostic significance of EZH2 in several human cancers. However, the clinical signature and further mechanisms of EZH2 function in gliomagenesis are still poorly understood. In this study, we found that increased EZH2 expression was associated with tumor grade. High expression of EZH2 in GBM was determined to be a strong and independent predictor of short overall survival. Further, we screened EZH2 targets and associated genes in GBM. Repression of EZH2 induced cell cycle arrest and inhibited tumor growth in vivo. This event represents a positive feedback loop with β-catenin/TCF4 and STAT3 signaling. Taken together, EZH2 could be an independent prognostic factor and potential therapeutic target for GBM.

Keywords: EZH2; Glioblastoma; Prognostic biomarker; Tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cell Cycle Checkpoints
  • Cell Movement
  • Cell Proliferation
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / blood supply*
  • Glioblastoma / metabolism
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Mice, Nude
  • Neoplasm Grading
  • Neovascularization, Pathologic*
  • Oligonucleotide Array Sequence Analysis
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2