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

Junxia Zhang; Luyue Chen; Lei Han; Zhendong Shi; Jianning Zhang; Peiyu Pu; Chunsheng Kang

doi:10.1016/j.canlet.2014.11.003

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.

Authors

Junxia Zhang¹, Luyue Chen², Lei Han², Zhendong Shi², Jianning Zhang³, Peiyu Pu², Chunsheng Kang⁴

Affiliations

¹ Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Chinese Glioma Cooperative Group (CGCG), China.
² Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China; Chinese Glioma Cooperative Group (CGCG), China.
³ Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China.
⁴ Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China; Chinese Glioma Cooperative Group (CGCG), China. Electronic address: kang79061@gmail.com.

PMID: 25444902
DOI: 10.1016/j.canlet.2014.11.003

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