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.
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.
Authors: Andrew R Tsen; Patrick M Long; Heather E Driscoll; Matthew T Davies; Benjamin A Teasdale; Paul L Penar; William W Pendlebury; Jeffrey L Spees; Sean E Lawler; Mariano S Viapiano; Diane M Jaworski Journal: Int J Cancer Date: 2013-09-30 Impact factor: 7.396
Authors: Neha Kamran; Alexandra Calinescu; Marianela Candolfi; Mayuri Chandran; Yohei Mineharu; Antonela S Asad; Carl Koschmann; Felipe J Nunez; Pedro R Lowenstein; Maria G Castro Journal: Expert Opin Biol Ther Date: 2016-07-27 Impact factor: 4.388
Authors: Sriram Venneti; Mihir T Garimella; Lisa M Sullivan; Daniel Martinez; Jason T Huse; Adriana Heguy; Mariarita Santi; Craig B Thompson; Alexander R Judkins Journal: Brain Pathol Date: 2013-03-06 Impact factor: 6.508
Authors: Pierpaolo Peruzzi; Agnieszka Bronisz; Michal O Nowicki; Yan Wang; Daisuke Ogawa; Richard Price; Ichiro Nakano; Chang-Hyuk Kwon; Josie Hayes; Sean E Lawler; Michael C Ostrowski; E Antonio Chiocca; Jakub Godlewski Journal: Neuro Oncol Date: 2013-06-03 Impact factor: 12.300