title: RYBP predicts survival of patients with non-small cell lung cancer and regulates tumor cell growth and the response to chemotherapy.
abstract: 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 down-regulated 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.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Sukesh
authors.initials: S
authors.lastname: Voruganti
authors.affiliation: Department of Cancer Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; Department of Pharmacy, No. 401 Hospital of Chinese People's Liberation Army, Qingdao 266071, China.
authors.forename: Fangxiu
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Jiang-Jiang
authors.initials: JJ
authors.lastname: Qin
authors.affiliation: Department of Cancer Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Sushanta
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Surgical Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA; Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Ming-Hai
authors.initials: MH
authors.lastname: Wang
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cancer Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: qianbiyun@shsmu.edu.cn.
authors.forename: Biyun
authors.initials: B
authors.lastname: Qian
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA; Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA. Electronic address: ruiwen.zhang@ttuhsc.edu.
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA; Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA. Electronic address: wwei.wang@ttuhsc.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D012097:Repressor Proteins; C120616:Rybp protein, mouse
keywords: Apoptosis; Chemotherapy; Non-small cell lung cancer; Patient survival; RYBP