miR-221/222调控上皮间质转化对甲状腺癌细胞131I（碘）代谢和靶向内放疗敏感性的影响及机制

分化型甲状腺癌失分化进展后对131I（碘）治疗抵抗，是甲状腺癌致死主要原因。逆转碘治疗抵抗是理想治疗方案，其中涉及碘代谢和靶向内放疗敏感性，两者在碘治疗过程中又相辅相成。通过现有miRNA表达谱和Oncomine数据库分析发现不同类型甲状腺癌中miR-221/222高表达，负向调控上皮间质转化（EMT）的基因SOCS3、TRPS1和TIMP3以及碘代谢相关基因低表达。经我们初步研究表明，甲状腺癌中miR-221/222调控EMT且SOCS3等为其潜在靶基因。本课题拟从miRNA研究着手，利用生物信息学、分子生物学、细胞和动物移植瘤模型等探讨其调控EMT机制及通过EMT调控对碘代谢和放疗敏感性影响并初步验证相关机制。甲状腺癌碘治疗抵抗细化为碘代谢和放疗敏感性两个层面，利于针对性的开展机制研究。通过miRNA又将二者结合，为深入的开展碘治疗抵抗机制研究和临床miRNA靶向治疗研究奠定基础。

Targeted radiation with 131I (iodine) is an effective treatment for differentiated thyroid cancer (DTC). De-differentiation of DTC cells results in a decline in iodine uptake and a reduced sensitivity to radiation, thus appearing resistance to iodine treatment. It is the current problem, which is urgently needed related research. Through analysis on miRNA profiles and Oncomine database, it is found that miR-221/222 are generally higher expressed and SOCS3, TRPS1, TIMP3 the negative regulators of epithelial-mesenchymal transition (EMT) and several iodine metabolism-related genes lower expressed in thyroid cancer(TC). EMT is a key mechanism influencing TC cell iodine uptake and sensitivity to tumor radiotherapy. Demonstration on TC cell lines, we found that miR-221/222 regulate EMT. Bioinformatics analysis identified that SOCS3, ect. are the potential target genes of miR-221/222. This topic uses bioinformatics tools and gene expression profiles analysis to screen the potential targeted genes. And molecular biology techniques and in vivo and in vitro experiments were used to verify targeted gene and its mechanism on iodine resistance. Based on the regulation of miRNA on EMT, this research tempts to restore the iodine metabolism in TC cells and improve their radiosensitivity, namely systematically resolves the two issues together and provides a new way for further clinical studies.