RYBP predicts survival of patients with non-small cell lung cancer and regulates tumor cell growth and the response to chemotherapy

被引:33
作者
Voruganti, Sukesh [1 ]
Xu, Fangxiu [2 ,3 ]
Qin, Jiang-Jiang [1 ]
Guo, Yan [2 ]
Sarkar, Sushanta [1 ]
Gao, Ming [4 ]
Zheng, Zhijie [5 ]
Wang, Ming-Hai [6 ,7 ]
Zhou, Jianwei [8 ]
Qian, Biyun [2 ,5 ]
Zhang, Ruiwen [1 ,7 ]
Wang, Wei [1 ,7 ]
机构
[1] Texas Tech Univ, Sch Pharm, Dept Pharmaceut Sci, Hlth Sci Ctr, Amarillo, TX 79106 USA
[2] Tianjin Med Univ, Canc Inst & Hosp, Dept Canc Epidemiol & Biostat, Tianjin 300060, Peoples R China
[3] Chinese Peoples Liberat Army, Hosp 401, Dept Pharm, Qingdao 266071, Peoples R China
[4] Tianjin Med Univ, Canc Inst & Hosp, Dept Surg Oncol, Tianjin 300060, Peoples R China
[5] Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Hongqiao Int Inst Med,Fac Publ Hlth, Shanghai 200025, Peoples R China
[6] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Biomed Sci, Amarillo, TX 79106 USA
[7] Texas Tech Univ, Hlth Sci Ctr, Canc Biol Ctr, Amarillo, TX 79106 USA
[8] Nanjing Med Univ, Sch Publ Hlth, Dept Mol Cell Biol & Toxicol, Ctr Canc, Nanjing 210029, Jiangsu, Peoples R China
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
RYBP; Apoptosis; Chemotherapy; Non-small cell lung cancer; Patient survival; MDM2; INHIBITOR; IN-VITRO; POLYCOMB; INTERACTS; PROTEINS; DOMAIN; IDENTIFICATION; EXPRESSION; TARGET; RING1B;
D O I
10.1016/j.canlet.2015.09.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ring1 and YY1 binding protein (RYBP) is a member of the Polycomb group (PcG) proteins and regulates cell growth through both PcG-dependent and -independent mechanisms. Our initial study indicated that RYBP is down-regulated in human non-small cell lung cancer (NSCLC) tissues. The present study determined the molecular role of RYBP in the development of NSCLC We systemically investigated the association between the RYBP expression and the survival of patients with NSCLC. We also carried out in vitro and in vivo studies to explore the molecular basis for the tumor suppressor role of RYBP in NSCLC. Our clinical results demonstrated that the RYBP mRNA and protein expressions were significantly downregulated in NSCLC and significantly linked to the poor prognosis in NSCLC patients. The enforced expression of RYBP inhibited cell survival, induced apoptosis, and increased chemosensitivity in NSCLC cells; knockdown of RYBP showed the opposite effects. Moreover, adenoviral delivery of RYBP sensitized the NSCLC cells to chemotherapy in vivo. In addition, RYBP expression was induced by paclitaxel, the first-line chemotherapeutic agent for NSCLC. Our results reveal that RYBP inhibits the aggressiveness of NSCLC cells and downregulation of RYBP is associated with poor prognosis, suggesting that RYBP could be developed as a biomarker and a novel target for therapy in patients with lung cancer. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:386 / 395
页数:10
相关论文
共 32 条
[1]   The Polycomb-associated protein Rybp is a ubiquitin binding protein [J].
Arrigoni, Rachele ;
Alam, Steven L. ;
Wamstad, Joseph A. ;
Bardwell, Vivian J. ;
Sundquist, Wesley I. ;
Schreiber-Agus, Nicole .
FEBS LETTERS, 2006, 580 (26) :6233-6241
[2]   The Drosophila RYBP gene functions as a Polycomb-dependent transcriptional repressor [J].
Bejarano, F ;
González, I ;
Vidal, M ;
Busturia, A .
MECHANISMS OF DEVELOPMENT, 2005, 122 (10) :1118-1129
[3]   Polycomb group proteins: navigators of lineage pathways led astray in cancer [J].
Bracken, Adrian P. ;
Helin, Kristian .
NATURE REVIEWS CANCER, 2009, 9 (11) :773-784
[4]   RYBP stabilizes p53 by modulating MDM2 [J].
Chen, Deng ;
Zhang, Jianbing ;
Li, Mao ;
Rayburn, Elizabeth R. ;
Wang, Hui ;
Zhang, Ruiwen .
EMBO REPORTS, 2009, 10 (02) :166-172
[5]   Human death effector domain-associated factor interacts with the viral apoptosis agonist Apoptin and exerts tumor-preferential cell killing [J].
Danen-van Oorschot, AAAM ;
Voskamp, P ;
Seelen, MCMJ ;
van Miltenburg, MHAM ;
Bolk, MW ;
Tait, SW ;
Boesen-de Cock, JGR ;
Rohn, JL ;
Borst, J ;
Noteborn, MHM .
CELL DEATH AND DIFFERENTIATION, 2004, 11 (05) :564-573
[6]  
Fang BL, 2003, CURR OPIN MOL THER, V5, P475
[7]   RYBP, a new repressor protein that interacts with components of the mammalian Polycomb complex, and with the transcription factor YY1 [J].
García, E ;
Marcos-Gutiérrez, C ;
Lorente, MDM ;
Moreno, JC ;
Vidal, M .
EMBO JOURNAL, 1999, 18 (12) :3404-3418
[8]   Yeast two-hybrid cloning of a novel zinc finger protein that interacts with the multifunctional transcription factor YY1 [J].
Kalenik, JL ;
Chen, DG ;
Bradley, ME ;
Chen, SJ ;
Lee, TC .
NUCLEIC ACIDS RESEARCH, 1997, 25 (04) :843-849
[9]   Adenovirus-based cancer gene therapy [J].
Kaplan, JM .
CURRENT GENE THERAPY, 2005, 5 (06) :595-605
[10]   Identification of eight candidate target genes of the recurrent 3p12p14 loss in cervical cancer by integrative genomic profiling [J].
Lando, Malin ;
Wilting, Saskia M. ;
Snipstad, Kristin ;
Clancy, Trevor ;
Bierkens, Mariska ;
Aarnes, Eva-Katrine ;
Holden, Marit ;
Stokke, Trond ;
Sundfor, Kolbein ;
Holm, Ruth ;
Kristensen, Gunnar B. ;
Steenbergen, Renske D. M. ;
Lyng, Heidi .
JOURNAL OF PATHOLOGY, 2013, 230 (01) :59-69