碘诱导细胞自噬对甲状腺乳头状癌的影响及分子机制

结题报告

项目介绍

AI项目解读

基本信息

批准号：
81673108
项目类别：
面上项目
资助金额：
60.0万
负责人：
乔虹
依托单位：
哈尔滨医科大学
学科分类：
H3013.地方病学
结题年份：
2020
批准年份：
2016
项目状态：
已结题
起止时间：
2017-01-01 至2020-12-31

项目参与者：
张德新；张守臣；张延清；陈美君；韩珺；魏艳军；许晓娜；郝明瑜；
关键词：
信号通路甲状腺癌自噬碘环境因素

项目摘要

The prevalence of papillary thyroid carcinoma (PTC) is high, with a high rate of recurrence and concealment. Researches shows that iodine can affect the biologic behavior of PTC cells through inducing gene mutation, changing activity of cytokines, regulating apoptosis related protein expression and so on. Autophagy is an important link in the occurrence and development of PTC. Therefore, it is necessary to investigate the effect and the mechanism of iodine on PTC through effecting autophagy. Our previous work found that different iodine concentration affected the autophagy level as well as the viability of PTC cells. In addition, we found out differentially expressed genes and their functions based on the RNA-Seq date of patients. On this basis, we plan to research the influence of iodine on PTC cells by effecting autophagy from the point of morphology to molecular biology; To find out signaling pathways and key genes related to PTC cell autophagy induced by iodine through taking advantage of bioinformatics method; To observe the regulating effect of the signaling pathway on PTC cells autophagy by over expression and knocking out the key genes at cellular level; To investigate the relationship between iodine concentration, tumors size and signaling pathway in vivo experiment ( nude mice and PTC patients). Through the above work, we will reveal the effect and molecular mechanism of iodine on PTC by inducing autophagy. And then we will look for the iodine concentration that intervene the development and improve the prognosis of PTC as well as lay the foundation of preventing the recurrence and deterioration of PTC.

甲状腺乳头状癌（PTC）患病率高、复发率高、隐匿性强。研究证实碘可以诱发基因突变、改变细胞因子活性和调控凋亡蛋白表达等影响PTC细胞的生物学行为，自噬也是参与PTC发生发展的重要环节，因此，研究碘通过细胞自噬影响PTC的发展及机制非常必要。我们的前期工作发现碘浓度影响PTC细胞自噬水平，也改变了其增殖能力；并基于PTC患者RNA-Seq数据挖掘出差异表达基因及其功能。在此基础上，本项目拟从形态学到分子生物学观察碘诱导自噬影响PTC细胞的生物学行为；利用生物信息学方法挖掘碘诱导PTC细胞自噬的信号通路和关键基因；并利用过表达和敲除关键基因的方法，在细胞水平观察信号通路对PTC细胞自噬的调控作用；进一步通过体内实验（裸鼠和PTC病人）研究碘浓度和瘤体大小及信号通路的相关性。通过以上工作揭示碘诱导自噬对PTC的影响及分子机制，为寻找干预PTC发展的碘浓度，改善预后，防止PTC复发和恶化奠定基础。

结项摘要

甲状腺乳头状癌（PTC）患病率高、复发率高、隐匿性强。研究证实碘可以诱发基因突变、改变细胞因子活性和调控凋亡蛋白表达等影响PTC细胞的生物学行为，自噬也是参与PTC发生发展的重要环节，因此，研究碘通过细胞自噬影响PTC的发展及机制非常必要。本项目发现碘浓度影响PTC细胞自噬水平，也改变了其增殖能力。在此基础上，项目明确了碘对PTC细胞生物学行为的影响，揭示碘通过诱导细胞自噬影响PTC的发展及其分子机制，阐明尿碘水平与PTC患者肿瘤特征的关系，并筛查出6个甲状腺乳头状癌的分子标记物。为寻找干预PTC发展的碘浓度，改善预后，防止PTC复发和恶化奠定基础。