新效正抑癌候选基因NESG1在鼻咽癌中功能鉴定及其分子基础初步研究

项目名称： 新效正抑癌候选基因NESG1在鼻咽癌中功能鉴定及其分子基础初步研究

项目编号： No.30870973

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 方唯意

作者单位： 南方医科大学

项目金额： 32万元

中文摘要： NESG1基因是1999年姚开泰教授领导的课题组发现和克隆的一个新基因。2005年，我们重新克隆该序列发现该基因序列存在两个错误位点。随后，我们校正了该基因，并初步发现该基因在鼻咽癌中表达下调。随后的研究主要针对该基因在鼻咽癌中的表达情况、功能、初步的分子机制以及该基因在鼻咽癌中表达下调是否存在着启动子甲基化情况进行了研究。我们的结果显示，NESG1在鼻咽癌中表达明显下调，过表达的NESG1和抑制NESG1表达后能分别抑制和恢复鼻咽癌细胞增殖、游走和侵袭能力，并参与细胞周期的调控。分子机制分析显示，NESG1能通过参与调控细胞周期因子p21和CCNA1的表达来参与细胞周期的调控。蛋白质组分析显示，NESG1能调节多个蛋白因子，其具体调控机制还有待进行研究。此外，鼻咽癌组织全基因组甲基化谱基因芯片分析显示，NESG1启动子区域并无甲基化的发生。

中文关键词： 关键词：NESG1；鼻咽癌；候选抑癌基因；

英文摘要： NESG1 as a new gene was cloned from human nasopharynx epithelium by Prof.Yao's research group in 1999 years.Recently,we found that the original submitted sequence of NESG1 existed the substitution and deletion mutation of nucleotide after we recloned this gene. Subsequently, we revised this gene and found that NESG1 was downregulated in NPC. In the later research, the expression, function, preliminarily molecular mechanism, and promoter methylation of NESG1 were examined by us. Our results demonstrated that NESG1 expression was decreased in NPC. Overexpression of NESG1 and suppressing NESG1 expression inhibited or restoried respectively the ability of cell proliferation,migration,invasion, and participating the regulation of cell cycle in NPC. Molecular mechanism showed that NESG1 regulated cell cycle via cell cycle factor p21 and CCNA1.Proteomics analysis indicated that NESG1 was involved in controlling the expression of a few protein factors. However, its detailed mechanisms is still to be demonstrated. Finally, NimbleGen DNA methylation microarray to assess its methylation status in 17 NPC cases. However, there were no significant changes in NESG1 promoter methylation observed in these samples, suggesting other mechanisms were involved in the repression of NESG1 in NPC.

英文关键词： NESG1;Nasopharyngeal carcinoma;Potential tumor suppressor gene