Epigenetic repression of regulator of G-protein signaling 2 by ubiquitin-like with PHD and ring-finger domain 1 promotes bladder cancer progression

作者: Liang Ying , Jun Lin , Feng Qiu , Ming Cao , Haige Chen

DOI: 10.1111/FEBS.13116

关键词:

摘要: Ubiquitin-like with PHD and ring-finger domain 1 (UHRF1) binds to methylated promoters of tumor-suppressor genes suppresses gene expression by forming complexes DNA methyltransferases. Recent studies have shown that repression regulator G-protein signaling (RGS) 2 increases cancer cell growth. However, little is known about whether UHRF1 promotes bladder progression epigenetic silencing RGS2. Here, we show increased in lines most tissues as compared normal controls. overexpression proliferation, whereas inhibition proliferation. In cells, inhibits RGS2 increasing the methylation CpG nucleotides promoter. analysis showed tumor-specific TGS2 promoter 73% (38/52) tumors. High correlated aberrant tumors, which results loss expression, confirmed demethylation lines. Functionally, re-expression partly abrogates UHRF1-induced Furthermore, Kaplan–Meier low significantly reduced overall survival patients cancer. These demonstrate contributes progression.

参考文章(25)
Richard R. Neubig, Huailing Zhong, Regulator of G protein signaling proteins: novel multifunctional drug targets. Journal of Pharmacology and Experimental Therapeutics. ,vol. 297, pp. 837- 845 ,(2001)
David M. Berman, Yunfei Wang, Zhengyu Liu, Qiong Dong, Lorri-Anne Burke, Lance A. Liotta, Rory Fisher, Xifeng Wu, A functional polymorphism in RGS6 modulates the risk of bladder cancer. Cancer Research. ,vol. 64, pp. 6820- 6826 ,(2004) , 10.1158/0008-5472.CAN-04-1916
M Unoki, J D Kelly, D E Neal, B A J Ponder, Y Nakamura, R Hamamoto, UHRF1 is a novel molecular marker for diagnosis and the prognosis of bladder cancer British Journal of Cancer. ,vol. 101, pp. 98- 105 ,(2009) , 10.1038/SJ.BJC.6605123
Zheng Jiang, Zhimin Wang, Ye Xu, Beilan Wang, Wei Huang, Sanjun Cai, Analysis of RGS2 expression and prognostic significance in stage II and III colorectal cancer. Bioscience Reports. ,vol. 30, pp. 383- 390 ,(2010) , 10.1042/BSR20090129
Julie A. Law, Steven E. Jacobsen, Establishing, maintaining and modifying DNA methylation patterns in plants and animals Nature Reviews Genetics. ,vol. 11, pp. 204- 220 ,(2010) , 10.1038/NRG2719
L Sabatino, A Fucci, M Pancione, V Carafa, A Nebbioso, C Pistore, F Babbio, C Votino, C Laudanna, M Ceccarelli, L Altucci, I M Bonapace, V Colantuoni, UHRF1 coordinates peroxisome proliferator activated receptor gamma (PPARG) epigenetic silencing and mediates colorectal cancer progression. Oncogene. ,vol. 31, pp. 5061- 5072 ,(2012) , 10.1038/ONC.2012.3
John H Kehrl, Srikumar Sinnarajah, RGS2: a multifunctional regulator of G-protein signaling. The International Journal of Biochemistry & Cell Biology. ,vol. 34, pp. 432- 438 ,(2002) , 10.1016/S1357-2725(01)00141-8
Raju Kandimalla, Angela A. van Tilborg, Ellen C. Zwarthoff, DNA methylation-based biomarkers in bladder cancer Nature Reviews Urology. ,vol. 10, pp. 327- 335 ,(2013) , 10.1038/NRUROL.2013.89
Feng Wang, Yong-Zhi Yang, Chen-Zhang Shi, Peng Zhang, Mary Pat Moyer, Hui-Zhen Zhang, Yang Zou, Huan-Long Qin, UHRF1 Promotes Cell Growth and Metastasis Through Repression of p16 ink4a in Colorectal Cancer Annals of Surgical Oncology. ,vol. 19, pp. 2753- 2762 ,(2012) , 10.1245/S10434-011-2194-1
Karen Chiam, Carmela Ricciardelli, Tina Bianco-Miotto, Epigenetic biomarkers in prostate cancer: Current and future uses Cancer Letters. ,vol. 342, pp. 248- 256 ,(2014) , 10.1016/J.CANLET.2012.02.011