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.

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.
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RYBP 表达与肝细胞癌 (HCC) 患者的更好生存以及 HCC 细胞体外和体内化疗的反应性相关。

DOI:
10.18632/oncotarget.2598
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发表时间:
2014-11-30
期刊:
影响因子:
--
通讯作者:
Zhang R
Zhang R
中科院分区:
其他
文献类型:
--
作者:
Wang W;Cheng J;Qin JJ;Voruganti S;Nag S;Fan J;Gao Q;Zhang R

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RYBP是多梳蛋白群(polycomb group, PcG)的一员,通常通过染色质的表观遗传修饰作为转录抑制因子。本研究旨在探讨RYBP在HCC进展、化疗敏感性和患者生存中的作用,并探讨其潜在的分子机制。在这项研究中,我们研究了RYBP在400对人类HCC组织和匹配的非癌样本中的表达。在体外和体内研究RYBP对HCC肿瘤生长转移和化疗敏感性的影响。我们在此证明RYBP在HCC组织样本中的表达明显低于匹配的非癌性肝组织。在临床上,RYBP的低表达是HCC患者预后不良的独立预测因子。在体外HCC模型中,强化RYBP表达抑制细胞生长和侵袭,诱导细胞凋亡,增加细胞的化学敏感性,而下调RYBP则相反。此外,顺铂诱导RYBP表达,腺病毒介导的RYBP表达抑制HCC肿瘤生长,使HCC对体内常规化疗敏感。我们的研究结果表明,在癌细胞中重新激活RYBP可能为HCC治疗提供一种有效和安全的治疗方法。
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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