ING3：原发性肝癌的诊断与治疗新靶点

项目名称： ING3：原发性肝癌的诊断与治疗新靶点

项目编号： No.81201877

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 杨海彦

作者单位： 哈尔滨医科大学

项目金额： 23万元

中文摘要： ING3是新发现的候选抑癌基因，在多种人类肿瘤中表达失调。已发现ING3影响肿瘤细胞增殖与凋亡、调节染色体构象、调控基因表达，影响P53及细胞信号通路活性，但在原发性肝癌中的研究还未见报道。本研究欲探讨ING3在原发性肝癌中的表达、功能及其作用机理，包括以下内容：一、研究ING3在原发性肝癌中的表达及临床意义，进而研究ING3在原发性肝癌中表达失调的机制；二、肝癌细胞中ING3的异位表达与沉默，通过体外和体内研究观察ING3过表达或沉默后，肝癌细胞的生物学行为变化，探讨其在原发性肝癌中的功能。三、通过蛋白质芯片筛选ING3的上下游蛋白，进而结合功能实验，验证ING3的上下游蛋白及其介导的信号转导通路，通过Real-time PCR芯片研究ING3调控的microRNA，最终明确ING3在原发性肝癌中作用的分子机理。本课题研究成功，将为原发性肝癌提供新的诊断学指标和分子治疗靶点。

中文关键词： 肝细胞癌；肿瘤抑制因子-3；预后；机制；超甲基化癌基因-1

英文摘要： ING3, a novel tumor-suppressor, has been shown to be involved in tumor transcriptional regulation, apoptosis, cell cycle，chromatin remodeling, and activation of cell signlalling pathways. Some studies have demonstrated that ING3 is dysregulated in several types of cancers. However, the role of ING3 in primary hepatic cancer (PHC) remains largely unclear. In the present research, we aimed to investigate the expression, function and molecular mechnism of ING3 protein in PHC. The research includes three parts: 1. Investigating the expression, clinical significance and inactivation mechnism of ING3 in PHC. 2. Observing the biological behaviour changing of hepatic cancer cells after ING3 ectopic expression and silencing in vivo and vitro. 3. Screening the upstream and downstream proteins by protein microarray and prooving ING3 plays roles in hepatic cancer cells through regulating downstream proteins and their mediated signal transduction pathways, then screening the mircroRNAs regulated by ING3 with the method of Real-time PCR microarray analysis and finnally confirming the molecular mechanisms of ING3 in PHC. The success of this research will provide a new diagnostic marker and a potential molecular therapeutic target for PHC.

英文关键词： HCC；ING3；prognosis；mechnism；HIC1