CBX8促进肝癌细胞增殖的分子机制研究

项目名称： CBX8促进肝癌细胞增殖的分子机制研究

项目编号： No.81502388

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 周璇

作者单位： 青岛大学

项目金额： 19万元

中文摘要： 肝细胞癌恶性程度高，预后差，其发生发展机制尚未完全阐明。已有研究表明，多梳基因家族蛋白（PcG）与肿瘤发生发展关系密切。我们在前期研究中发现多梳基因家族蛋白CBX8在肝癌中呈显著高表达，且与不良预后相关；基因芯片结果表明在肝癌细胞中沉默CBX8，p53下游靶基因表达上调，并显著抑制肝癌细胞增殖能力；体外实验表明CBX8与p53存在直接相互结合。本项目拟沉默或过表达CBX8，在细胞水平、动物模型中，研究CBX8在肝癌中的作用，并明确其可能的机制是通过调控p53信号通路。同时，在肝癌组织标本中探讨CBX8/p53通路的临床意义，从而明确CBX8可能通过调控p53通路促进肝癌细胞增殖的新机制，为诠释肝癌发生发展的分子机制和寻找肿瘤治疗新靶点提供有力的科学依据。

中文关键词： 肝细胞肝癌；CBX8；p53；增殖

英文摘要： Hepatocellular carcinoma (HCC) is a highly malignant tumor with very poor prognosis. However, the molecular mechanisms underlying HCC progression remain largely unknown. Increasingly evidences have demonstrated that the PcG contributed to tumorigenesis and played important roles in the malignant progression of tumors. Recently, we found that the expression of CBX8 in HCC tissues was significantly higher than those in the adjacent tissues and overexpression of CBX8 indicated a poor overall survival. We also found that silencing CBX8 made p53-targeted genes increasing and inhibited the proliferation of HCC cells significantly. Exogenous CBX8 combined with p53 directly. In our study, we aim to explore the role of CBX8 in HCC and clear that the mechanism may be through the regulation of p53 pathway, and to elucidate the expression and clinical significance of CBX8/p53 in HCC tissues. We propose a new mechanism that CBX8 promotes the proliferation of HCC cells through the regulation of p53 pathway. Our study may provide a new idea of the molecular mechanism underlying HCC progression and a novel potential therapeutic target for the comprehensive HCC treatment.

英文关键词： HCC;CBX8;p53;proliferation