eIF1AX通过启动CD147翻译促进女性甲状腺乳头状癌发生发展的机制研究

The incidence of papillary thyroid carcinoma (PTC) is increasing year by year, and there is a gender difference of 1:3 between men and women worldwide. Studying the high incidence of women helps to understand the gender differences in PTC. We have confirmed that CD147 plays an important role in the development of PTC. Our preliminary results have found that the abnormal expression of eIF1AX, a transcription product of the X-linked gene EIF1AX, is closely related to female PTC, and regulates the expression of CD147 at the translational level. This project intends to further investigate the relationship between eIF1AX expression level and female PTC through case-control study, then analyze the function of eIF1AX at the cell and animal level, and clarify the mechanism of eIF1AX regulating CD147 through yeast two-hybrid system and GST pull-down experiments. This project aims to clarify the role of eIF1AX in the pathogenesis of female PTC, with a view to further understanding the causes of gender differences in PTC, and to provide a scientific basis for the screening and prevention of high-risk women with PTC.

甲状腺乳头状癌（papillary thyroid carcinoma，PTC）的发病率呈逐年增长的趋势，并在全球范围内普遍存在男女比例1:3的性别差异，研究女性高发的机制有助于理解PTC发病的性别差异。我们已经证实CD147在PTC发生发展中起重要作用，预实验发现X染色体连锁基因EIF1AX的转录产物eIF1AX异常表达与女性PTC密切相关，并在翻译水平调控CD147的表达。本项目拟通过病例-对照研究，进一步查明eIF1AX表达水平与女性PTC发病的关系；进而在细胞及动物水平对eIF1AX的功能进行分析，并通过酵母双杂交系统及GST pull-down等实验，明确eIF1AX调控CD147的机制。本项目旨在阐明eIF1AX在女性PTC发病中的作用，以期进一步理解PTC发病性别差异的原因，同时，为女性PTC高危人群的筛选和预防提供科学依据。

甲状腺乳头状癌（papillary thyroid carcinoma，PTC）的发病率呈逐年增长的趋势，并在全球范围内普遍存在男女比例1:3的性别差异，研究女性高发的机制有助于理解PTC发病的性别差异。我们前期预实验提示X染色体连锁基因EIF1AX的转录产物eIF1AX在女性PTC组织中特异性高表达，可能是女性PTC发病的关键调控点。本项目从体外和体内分别进行描述性和干预性研究，以女性PTC临床组织及细胞株为研究对象，并以EIF1AX为研究靶点，查明eIF1AX表达水平与女性PTC发病的关系，并进一步明确eIF1AX调控PTC性别差异的作用和机制。我们的体内和体外实验结果显示，eIF1AX的表达水平对女性PTC的发生至关重要。目前的研究表明，过表达eIF1AX显著促进女性PTC细胞的增殖、侵袭和转移能力，但在男性PTC细胞中的功能相反；机制方面，EIF1AX通过Akt-mTOR信号通路调控女性PTC的增殖能力。本研究成果有助于进一步理解PTC发病性别差异的原因，同时，为女性PTC高危人群的筛选和预防提供科学依据。