title: Enhancer of zeste homolog 2 (EZH2) promotes tumour cell migration and invasion via epigenetic repression of E-cadherin in renal cell carcinoma.
abstract: OBJECTIVE
  To investigate the molecular mechanism and clinical significance for an oncogenic role of enhancer of zeste homolog 2 (EZH2) in renal cell carcinoma (RCC).
  
  
  METHODS
  Immunohistochemistry analyses of EZH2, histone H3 trimethyl Lys27 (H3K27me3) and E-cadherin were performed in tumour tissue samples from 257 patients with RCC. Regulatory effects of EZH2 on E-cadherin expression were examined by quantitative real-time polymerase chain reaction, Western blot, chromatin immunoprecipitation assay and immunohistochemical staining. Migration and invasion assays were performed in RCC cell lines. Tumour xenograft experiments with RCC cells were carried out in nude mice.
  
  
  RESULTS
  EZH2 promoted migration and invasion in RCC cell lines. Silencing EZH2 with short-hairpin EZH2 (shEZH2) or 3-deazaneplanocin A (DZNep) inhibited migration and invasion (P < 0.001), up-regulated the expression of E-cadherin in vitro, inhibited tumour growth, and prolonged survival in vivo (P = 0.022). EZH2 expression accompanied with E-cadherin repression was associated with advanced disease stage (P = 0.004) and poor overall (P < 0.001) and disease-free survival (P < 0.001).
  
  
  CONCLUSIONS
  EZH2 may contribute to RCC progression and is a potential therapeutic target for advanced RCC.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Qilai
authors.initials: Q
authors.lastname: Long
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Guo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000187:drug effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D047369:Chromatin Immunoprecipitation; D018572:Disease-Free Survival; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D063151:Polycomb Repressive Complex 2 / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015820:Cadherins; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2
keywords: DZNep; EMT; EZH2; RCC; kidney cancer; survival