白介素13在甲状腺乳头状癌发生中的作用与调控机制

项目名称： 白介素13在甲状腺乳头状癌发生中的作用与调控机制

项目编号： No.81472501

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 蔚青

作者单位： 同济大学

项目金额： 75万元

中文摘要： 甲状腺乳头状癌(PTC)是最常见的内分泌癌，其发病机制并不十分明了。我们前期研究表明泛素羧基末端水解酶L5(UCH-L5)和白介素13(IL-13)在PTC中过量表达，并证实UCH-L5与IL-13可能存在相互作用，UCH-L5正向调控IL-13蛋白含量。根据以往实验基础和相关文献报道，我们提出如下假说：UCH-L5通过与核内底物蛋白IL-13相互作用，导致IL-13去泛素化程度增加而聚积；IL-13与UCH-L5相互作用形成复合物出核，进而激活转录因子AP-1和STAT6，使下游癌蛋白增加，从而促进细胞增殖、抑制细胞凋亡，导致PTC发生发展。本项目拟探讨UCH-L5和IL-13在PTC中的表达及临床意义；验证UCH-L5和IL-13在PTC发生发展中的作用；明确UCH-L5和IL-13的相互作用，阐明UCH-L5和IL-13参与PTC发生发展的分子机制，为PTC的诊断和治疗提供理论依据。

中文关键词： 甲状腺乳头状癌；细胞增殖；细胞凋亡；白介素13；去泛素化

英文摘要： Along with the increase of incidence rate of papillary thyroid carcinoma (PTC), the diagnostic and therapeutic tools that aimed directly at etiological factors were needed imperiously. Deubiquitinase plays an important role in the regulation of protein degradation, which involved in many types of cancer initiation and progress. Our previous studies have shown that express level of ubiquitin carboxyl-terminal hydrolase L5 (UCH-L5) and interleukin-13 (IL-13) were relatively higher in PTC than those in normal thyroid tissue. The interaction between UCH-L5 and IL-13 was also confirmed. UCH-L5 may mediate the protein level of IL-13 through deubiquitination. Based on our experimental results and previous reports in the literature, we hypothesized that overexpression of UCH-L5 could induce deubiquitination of the substrate protein IL-13 and increases its accumulation through their interaction. UCH-L5 then interacts with IL-13 to form a nuclear complex and accelerates IL-13 nuclear export to give rise to cell cycle disorders and abnormal cell proliferation, thus resulting to the development of PTC. This project will detect the levels of UCH-L5 and IL-13 in PTC, assess their clinical significance, validate the role of UCH-L5 and PTC in development of PTC and further clarify their interactions of UCH-L5 and IL-13 and the molecular mechanism of UCH-L5-induced IL-13 deubiquitination in tumorigenesis of PTC to provide a theoretical basis for PTC diagnosis and treatment.

英文关键词： PTC;Proliferation;Apoptosis;Interleukin-13;Deubiquitination