title: RYBP expression is associated with better survival of patients with hepatocellular carcinoma (HCC) and responsiveness to chemotherapy of HCC cells in vitro and in vivo.
abstract: RYBP is a member of the polycomb group (PcG) proteins that typically act as transcriptional repressors via epigenetic modification of chromatin. The present study was designed to investigate the role of RYBP in HCC progression, chemosensitivity, and patient survival, and to explore the underlying molecular mechanism(s). In this study we investigated the expression of RYBP in 400 pairs of human HCC tissues and matched noncancerous samples. The effects of RYBP on HCC tumor growth and metastasis and chemosensitivity were determined both in vitro and in vivo. We herein demonstrate that the RYBP expression in HCC tissue samples was signiï¬cantly lower than that in matched noncancerous liver tissues. Clinically, the low expression of RYBP was an independent predictor of a poor prognosis in patients with HCC. In in vitro HCC models, enforced RYBP expression inhibited cell growth and invasion, induced apoptosis, and increased the chemosensitivity of the cells, while RYBP knockdown led to the opposite effects. Furthermore, RYBP expression was induced by cisplatin, and adenovirus-mediated RYBP expression inhibited HCC tumor growth and sensitized HCC to conventional chemotherapy in vivo. Our results demonstrate that reactivating RYBP in cancer cells may provide an effective and safe therapeutic approach to HCC therapy.
authors.affiliation: Department of Pharmaceutical Sciences, School of pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA. Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China. Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pharmaceutical Sciences, School of pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA. Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
authors.forename: Jiang-Jiang
authors.initials: JJ
authors.lastname: Qin
authors.affiliation: Department of Pharmaceutical Sciences, School of pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
authors.forename: Sukesh
authors.initials: S
authors.lastname: Voruganti
authors.affiliation: Department of Pharmaceutical Sciences, School of pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
authors.forename: Subhasree
authors.initials: S
authors.lastname: Nag
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China. Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China. Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Sciences, School of pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA. Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D015999:Multivariate Analysis; D009368:Neoplasm Transplantation; D011379:Prognosis; D012097:Repressor Proteins; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C434957:RYBP protein, human; D012097:Repressor Proteins; D002945:Cisplatin