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	Wei Wang, Jianwen Cheng, Jiang-Jiang Qin, Sukesh Voruganti, Subhasree Nag, Jia Fan, Qiang Gao, Ruiwen Zhang
Journal	Oncotarget (Oncotarget) Vol. 5 Issue 22 Pg. 11604-19 (Nov 30 2014) ISSN: 1949-2553 [Electronic] United States
PMID	25344099 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Biomarkers, Tumor Intracellular Signaling Peptides and Proteins RYBP protein, human Repressor Proteins Cisplatin
Topics	Adenoviridae (genetics) Animals Antineoplastic Agents (therapeutic use) Apoptosis Biomarkers, Tumor (metabolism) Carcinoma, Hepatocellular (drug therapy, metabolism) Cell Line, Tumor Cisplatin (chemistry) Combined Modality Therapy Disease Progression Disease-Free Survival Down-Regulation Female Gene Expression Regulation, Neoplastic Hep G2 Cells Humans Intracellular Signaling Peptides and Proteins (metabolism) Liver Neoplasms (drug therapy, metabolism) Mice Mice, Nude Multivariate Analysis Neoplasm Transplantation Prognosis Repressor Proteins Tissue Array Analysis Treatment Outcome

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