Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells

F. Orzan, S. Pellegatta, P. L. Poliani, F. Pisati, V. Caldera, F. Menghi, D. Kapetis, C. Marras, D. Schiffer, G. Finocchiaro

Research output: Contribution to journalArticle

Abstract

Aims: Proteins of the Polycomb repressive complex 2 (PRC2) are epigenetic gene silencers and are involved in tumour development. Their oncogenic function might be associated with their role in stem cell maintenance. The histone methyltransferase Enhancer of Zeste 2 (EZH2) is a key member of PRC2 function: we have investigated its expression and function in gliomas. Methods: EZH2 expression was studied in grade II-IV gliomas and in glioma stem-like cells (GSC) by quantitative PCR and immunohistochemistry. Effects of EZH2 down-regulation were analysed by treating GSC with the histone deacetylase (HDAC) inhibitor suberoylanide hydroxamic acid (SAHA) and by shRNA. Results: DNA microarray analysis showed that EZH2 is highly expressed in murine and human GSC. Real-time PCR on gliomas of different grade (n = 66) indicated that EZH2 is more expressed in glioblastoma multiforme (GBM) than in low-grade gliomas (P = 0.0013). This was confirmed by immunohistochemistry on an independent set of 106 gliomas. Treatment with SAHA caused significant up-regulation of PRC2 predicted target genes, GSC disruption and decreased expression of EZH2 and of the stem cell marker CD133. Inhibition of EZH2 expression by shRNA was associated with a significant decrease of glioma proliferation. Conclusion: The data suggest that EZH2 plays a role in glioma progression and encourage the therapeutic targeting of these malignancies by HDAC inhibitors.

Original languageEnglish
Pages (from-to)381-394
Number of pages14
JournalNeuropathology and Applied Neurobiology
Volume37
Issue number4
DOIs
Publication statusPublished - Jun 2011

    Fingerprint

Keywords

  • CD133
  • EZH2
  • Glioblastoma
  • Glioma stem-like cells
  • HDAC
  • Polycomb

ASJC Scopus subject areas

  • Geotechnical Engineering and Engineering Geology
  • Computational Mechanics
  • Mechanics of Materials
  • Materials Science(all)
  • Histology
  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Physiology (medical)
  • Neurology

Cite this