Li Liu1, Zhibing Xu1, Lei Zhong1, Hang Wang1, Shuai Jiang1, Qilai Long1, Jiejie Xu2, Jianming Guo1. 1. Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. 2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
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). MATERIALS AND 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). CONCLUSION: EZH2 may contribute to RCC progression and is a potential therapeutic target for advanced RCC.
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). MATERIALS AND 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). CONCLUSION:EZH2 may contribute to RCC progression and is a potential therapeutic target for advanced RCC.
Authors: Abhishek A Chakraborty; Eijiro Nakamura; Jun Qi; Amanda Creech; Jacob D Jaffe; Joshiawa Paulk; Jesse S Novak; Kshithija Nagulapalli; Samuel K McBrayer; Glenn S Cowley; Javier Pineda; Jiaxi Song; Yaoyu E Wang; Steven A Carr; David E Root; Sabina Signoretti; James E Bradner; William G Kaelin Journal: Sci Transl Med Date: 2017-07-12 Impact factor: 17.956
Authors: Hardik R Mody; Sau Wai Hung; Mohammad AlSaggar; Jazmine Griffin; Rajgopal Govindarajan Journal: Mol Cancer Res Date: 2016-09-13 Impact factor: 5.852