GOLM1（GP73）/TLR9途径抑制癌周干扰素产生促进肝癌转移恶性潜能机制研究

项目名称： GOLM1（GP73）/TLR9途径抑制癌周干扰素产生促进肝癌转移恶性潜能机制研究

项目编号： No.81502487

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： 郭磊

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 肝癌的转移复发与微环境免疫状态和肝癌细胞自身的转移特性密切相关。我们前期通过高通量基因组学筛选技术发现，GOLM1与肝癌转移恶性潜能密切联系；GOLPH2能够抑制肝癌患者术后干扰素治疗敏感性；其在癌组织表达与癌周免疫因子干扰素α、γ密切相关。基于蛋白-蛋白相互作用分析及前期研究提示，TLR9可能是GOLM1调控肝癌免疫炎症相关恶性潜能的关键中间衔接分子，由此提出“GOLM1-TLR9-IFNs-恶性潜能”功能轴这一新的分子机制。本课题拟在前期研究基础上，进一步围绕此功能轴展开以下研究：①分析肝癌细胞中GOLM1、TLR9、IFNs在表达和功能上的联系，对此功能轴进行验证；②在肝癌临床样本中检测GOLM1、TLR9、IFNs表达，探讨此功能轴与肝癌患者转移复发及预后的关系；③通过体内、体外实验，干预此功能轴，明确其对肝癌侵袭转移及免疫治疗抵抗的影响；为肝癌转移复发提供有效的预测模型干预靶点。

中文关键词： C09_肝和肝内胆管肿瘤；GOLM1(GP73)；干扰素；TLR9；肿瘤转移

英文摘要： It is well acknowledged that micro-environment as well as the characteristics of cancer cell itself are closely contributed to malignant phenotype in hepatocellular carcinoma (HCC).Previously, we had demonstrated that expression of GOLM1 was closely correlated with the malignant phenotype in HCC by means of a high-throughput genomic filtering technology. In-depth study, we found that GOLM1 can be used as a predictive serum marker for outcome of postoperative IFNα treatment in patients with hepatocellular carcinoma. Great significant association was found between higher levels of intratumoral GLOM1 and lower levels of peritumoral IFNs which had a significantly poorer prognosis. Based on our previous study about the protein interactions, we speculated that TLR9 may have an important role as a connected molecular between GOLM1 and the suppresed interferons (IFNs) in peritumoral hepatic tissues. So we suggest that there is a new molecular mechanism as an axis of GOLM1-TLR9-IFNs-malignant potential to take effect and we are going to carry out some researches on this functional axis as below: 1. Analyze the connection between the GOLM1, TLR9, IFNs, both structurally and functionally in HCC for the confirmation of this axis. 2. Determinate the expressions of these molecular in clinical specimens to investigate the correlation between this axis and recurrence，metastasis and poor prognosis of HCC patients. 3. Disturb this functional axis by some in vitro and in vivo assays for further validation that it can effectively predict the recurrence and serve as a potential therapeutic target in HCC.

英文关键词： hepatocellular carcinoma;GOLM1(GP73); interferons (IFNs);TLR9;cancer metastasis