肿瘤转移相关蛋白MTA1在核仁中的定位、功能及其与肿瘤的关系研究

项目名称： 肿瘤转移相关蛋白MTA1在核仁中的定位、功能及其与肿瘤的关系研究

项目编号： No.81502384

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： 刘健

作者单位： 首都医科大学

项目金额： 18万元

中文摘要： 肿瘤转移相关蛋白MTA1参与了众多肿瘤种恶性行为的调控过程，其机制至今依然不明。通过前期实验，我们首次发现并确认MTA1具有明显的核仁定位，推翻了以往关于MTA1在核仁中为阴性表达的结论。核仁功能与肿瘤的关系非常密切，提示MTA1可能通过调控核仁功能调控肿瘤的发生发展。文献报道DNA结合蛋白MTA1是一种核转录因子，提示核仁MTA1可能参与rDNA的转录调控。而前期co-IP、RNA-seq、DiClip-seq等实验还表明MTA1具有潜在的RNA加工剪切功能。因此本项目拟从新发现的核仁定位入手，分析MTA1在核仁中定位的分子机制，捕获并分析MTA1的核仁互作蛋白质组，探讨MTA1在rDNA转录、rRNA加工剪切中的功能机制，并从细胞、小鼠两个水平验证MTA1的核仁调控功能与肿瘤的关系，探讨MTA1在肿瘤治疗中的潜在应用价值。

中文关键词： 肿瘤转移相关蛋白；1；肿瘤；核仁定位；功能；分子机制

英文摘要： MTA1 is a tumor metastasis associated protein，involved in regulation of multiple tumor malignant behaviors, however, the mechanism is still unknown. By multiple molecular technologies of cell immunofluorescence, GFP tracing, immunoelectron microscopy and so on we first found and identified the localization of MTA1 in nucleolus, which overthrowed the previous conclusion that MTA1 is negative in nucleolus. Further investigation of the role of MTA1 in nucleolus will help to clarify the mechanism of MTA1 in cancer promotion. Paper analysis indicated that nuclear transcriptional factor MTA1 has multiple DNA binding regions and hence may play a role in rDNA transcriptional regulation. Moreover, much evidence by IP, RNA-seq、CLIP-seq and so on indicates that MTA1 has also a potential role in RNA processing regulation by binding to RNA. Following these clues, we, in this study, aim to investigate the function and mechanism of MTA1 in nucleolus, explore its role in cancer promotion, and evaluate the significance of MTA1 disruption in future cancer treatment.

英文关键词： MTA1;cancer;nucleolus localization;function;molecular mechanism