Functional roles of enhancer of zeste homolog 2 in gliomas.

Gliomas are the most common and lethal type of primary malignant brain tumor. Due to the infiltrative nature and high resistance to standard first line treatment with combinations of radiation and chemotherapy, the prognosis of patient is very poor. Recently, accumulated evidence suggests that enhancer of zeste homolog 2 (EZH2) serves as an oncogene and is involved in multiple glioma cell processes, including cell cycle, invasion, glioma stem cell maintenance, drug and radiotherapy resistance and so on. In this review, we will focus on updating current knowledge of EZH2 in gliomas. Moreover, the regulation of EZH2 by microRNAs and long non-coding RNAs and the therapeutic strategies targeting EZH2 for gliomas will also be discussed.

Yin Y ，Qiu S ，Peng Y 《-》

Epigenetic modification in gliomas: role of the histone methyltransferase EZH2.

Bian EB ，Li J ，He XJ ，Zong G ，Jiang T ，Li J ，Zhao B ... -  《-》

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

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. 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. 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. The data suggest that EZH2 plays a role in glioma progression and encourage the therapeutic targeting of these malignancies by HDAC inhibitors.

Orzan F ，Pellegatta S ，Poliani PL ，Pisati F ，Caldera V ，Menghi F ，Kapetis D ，Marras C ，Schiffer D ，Finocchiaro G ... -  《-》

Combined aberrant expression of Bmi1 and EZH2 is predictive of poor prognosis in glioma patients.

Bmi1 and EZH2 are involved in tumorigenesis of gliomas. However, clinicopathologic significance of their expression in gliomas is unknown; especially, the prognostic value of combined expression of Bmi1 and EZH2 has not been explored. Bmi1 and EZH2 expression in human gliomas and nonneoplastic brain tissues was measured by immunohistochemistry. Both Bmi1 and EZH2 expressions in glioma tissues were significantly higher than those in corresponding nonneoplastic brain tissues (both P<0.001). Additionally, the upregulations of Bmi1 and EZH2 proteins were both significantly associated with advanced WHO grades (both P<0.001) and low KPS (P=0.008 and 0.01, respectively). Moreover, the overall survival of patients with high Bmi1 protein expression (P=0.006) or high EZH2 protein expression (P=0.01) was obviously lower than those with low expressions. More interestingly, glioma patients with combined overexpression of Bmi1 and EZH2 proteins had the shortest overall survival (P<0.001). Furthermore, multivariate analysis showed that Bmi1n expression (P=0.02), EZH2 expression (P=0.03), and combined expression of Bmi1 and EZH2 (P=0.008), were all independent prognostic factors for overall survival in glioma patients. Our data suggest for the first time that the combination of Bmi1 and EZH2 overexpression may be a highly sensitive marker for the prognosis in glioma patients.

Wu Z ，Wang Q ，Wang L ，Li G ，Liu H ，Fan F ，Li Z ，Li Y ，Tu Y ... -  《-》

LncRNAs: new players in gliomas, with special emphasis on the interaction of lncRNAs With EZH2.

Gliomas are the most common primary malignancy in the brain, accounting for 50-60%. Despite all the efforts of cytoreductive surgery in combination with intense chemoradiotherapy, glioma remains an incurable disease. Recent studies have shown that long noncoding RNAs (lncRNAs) are involved in the pathology of gliomas. LncRNAs are involved in many cellular processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. In this review we focus on the dysregulation of lncRNAs in gliomas. We also address that epigenetic modification such as DNA methylation and microRNAs interact with lncRNAs in gliomas. In addition, the interaction of lncRNAs with signaling pathways in gliomas is discussed systematically, with particular emphasis on the interaction of lncRNAs with EZH2. Such approaches provide valuable insights into the potential future applications of lncRNAs in the treatment of gliomas.

Bian EB ，Li J ，Xie YS ，Zong G ，Li J ，Zhao B ... -  《-》