Oncotarget

Research Papers:

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

Wei Wang, Jianwen Cheng, Jiang-Jiang Qin, Sukesh Voruganti, Subhasree Nag, Jia Fan, Qiang Gao and Ruiwen Zhang _

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Oncotarget. 2014; 5:11604-11619. https://doi.org/10.18632/oncotarget.2598

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Abstract

Wei Wang1,2,*, Jianwen Cheng3,4,*, Jiang-Jiang Qin1,2,*, Sukesh Voruganti1, Subhasree Nag1, Jia Fan3,4, Qiang Gao3,4 and Ruiwen Zhang1,2

1 Department of Pharmaceutical Sciences, School of pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA

2 Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA

3 Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China

4 Institute of Biomedical Sciences, Fudan University, Shanghai, China

* These authors contributed to this work equally

Correspondence:

Ruiwen Zhang, email:

Qiang Gao, email:

Keywords: RYBP, Prognosis; Combination therapy; Apoptosis; HCC

Received: August 14, 2014 Accepted: October 18, 2014 Published: October 18, 2014

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 significantly 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.


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