The enhancer of zeste homolog 2 (EZH2), a potential therapeutic target, is regulated by miR-101 in renal cancer cells

被引:47
作者
Sakurai, Toshihiko [1 ]
Bilim, Vladimir N. [1 ]
Ugolkov, Andrey V. [3 ]
Yuuki, Kaori [1 ]
Tsukigi, Masaaki [1 ]
Motoyama, Teiichi [2 ]
Tomita, Yoshihiko [1 ]
机构
[1] Yamagata Univ, Sch Med, Dept Urol, Mol Oncol Lab, Yamagata 9909585, Japan
[2] Yamagata Univ, Sch Med, Dept Human Pathol, Dept Pathol 2, Yamagata 9909585, Japan
[3] Northwestern Univ, Chem Life Proc Inst, Ctr Dev Therapeut, Evanston, IL USA
基金
日本学术振兴会;
关键词
Renal cell carcinoma; Enhancer of zeste homolog 2; MicroRNA-101; GROUP PROTEIN EZH2; HISTONE METHYLTRANSFERASE; DNA METHYLATION; CARCINOMA; PROLIFERATION; EXPRESSION; GENE; OVEREXPRESSION; PROGRESSION; ROLES;
D O I
10.1016/j.bbrc.2012.05.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated a prognostic significance and the mechanism of aberrant nuclear expression of EZH2, a histone methyltransferase, in human renal cell carcinoma (RCC). We found nuclear EZH2 in 48 of 100 RCCs and it was significantly correlated with worse survival in RCC patients. We detected a decreased expression of miR-101 in 15 of 54 RCCs. We found that re-expression of miR-101 resulted in EZH2 depletion and decreased renal cancer cell proliferation. Our results show nuclear EZH2 as a prognostic marker of worse survival in human RCC, and identify miR-101 as a negative regulator of EZH2 expression and renal cancer cell proliferation. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:607 / 614
页数:8
相关论文
共 31 条
[1]   Polycomb group genes are targets of aberrant DNA methylation in renal cell carcinoma [J].
Avissar-Whiting, Michele ;
Koestler, Devin C. ;
Houseman, E. A. ;
Christensen, Brock C. ;
Kelsey, Karl T. ;
Marsit, Carmen J. .
EPIGENETICS, 2011, 6 (06) :703-709
[2]   Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions [J].
Bracken, AP ;
Dietrich, N ;
Pasini, D ;
Hansen, KH ;
Helin, K .
GENES & DEVELOPMENT, 2006, 20 (09) :1123-1136
[3]  
Bukowski R M, 2001, Semin Urol Oncol, V19, P148
[4]  
Bukowski RM, 1997, CANCER-AM CANCER SOC, V80, P1198, DOI 10.1002/(SICI)1097-0142(19971001)80:7<1198::AID-CNCR3>3.0.CO
[5]  
2-H
[6]   Systemic therapy for metastatic renal cell carcinoma in treatment naive patients: a risk-based approach [J].
Bukowski, Ronald M. .
EXPERT OPINION ON PHARMACOTHERAPY, 2010, 11 (14) :2351-2362
[7]   The role of EZH2 in tumour progression [J].
Chang, C-J ;
Hung, M-C .
BRITISH JOURNAL OF CANCER, 2012, 106 (02) :243-247
[8]  
Di Fiore F., 2012, BRIT J CANCER, V109, P1349
[9]   Expression of EZH2 and Ki-67 in colorectal cancer and associations with treatment response and prognosis [J].
Fluge, O. ;
Gravdal, K. ;
Carlsen, E. ;
Vonen, B. ;
Kjellevold, K. ;
Refsum, S. ;
Lilleng, R. ;
Eide, T. J. ;
Halvorsen, T. B. ;
Tveit, K. M. ;
Otte, A. P. ;
Akslen, L. A. ;
Dahl, O. .
BRITISH JOURNAL OF CANCER, 2009, 101 (08) :1282-1289
[10]   Oxidative stress, DNA methylation and carcinogenesis [J].
Franco, Rodrigo ;
Schoneveld, Onard ;
Georgakilas, Alexandros G. ;
Panayiotidis, Mihalis I. .
CANCER LETTERS, 2008, 266 (01) :6-11