探讨碘难治性分化型甲状腺癌（RAIR-DTC）分子机制、提高患者存活率，仍然是甲状腺癌研究的热点。近期，项目组在《Clin Transl Oncol》上报道外源性NIS可能是难治性肿瘤重要的作用靶点。结合文献分析及项目组前期研究，发现RAIR-DTC组织较DTC组织NIS蛋白表达显著减少，提示NIS表达改变可能是RAIR-DTC产生的机制之一。同时，项目组发现HMGB1在DTC组织中高表达，且HMGB1介导的自噬途径可以降低FTC-133细胞NIS的表达。本课题在上述研究基础上，提出了HMGB1介导的自噬下调NIS表达及其摄碘率可能是RAIR-DT产生的假说。针对上述假说，本项目拟采用多种先进研究手段，进一步深入系统的探讨HMGB1通过自噬调控FTC-133细胞NIS表达及摄碘的分子机制。开展本项目可望揭示HMGB1调控甲状腺癌细胞自噬的分子机制，为寻找RAIR-DTC靶向治疗提供新思路。

Radioiodine refractory differentiated thyroid cancer(RAIR-DTC) is a major obstacle to the successful treatment of thyroid carcinoma. Exploring the molecular mechanism of RAIR-DTC is still the topic in thyroid carcinoma research. Recently, our recent study demonstrated that exogenous sodium/iodide symporter（NIS）is a crucial regulator for treatment-resistant tumor therapy. Combined with data analysis and our former study, we found that NIS was expressed abundantly in RAIR-DTC compared with differentiated thyroid carcinoma (DTC), suggesting NIS played a potential contributory role in the pathogenesis in RAIR-DTC. Meanwhile, we also found that HMGB1 was expressed abundantly in DTC and HMGB1-medietaed autophagy induced NIS protein degradation in FTC133 cells. Based on these findings, our hypothesis is that HMGB1-mediated autophagy decreases NIS expression and radionuclide uptake contributing to the pathogenesis of RAIR-DTC. We will futherly determine whether HMGB1 regulated autophagy and NIS expression in FTC-133 cells and the signal pathways of HMGB1-mediated autophagy for RAIR-DTC . The fund supports the theory that HMGB1-mediated autophagy plays an important role in the tumorigenesis of RAIR-DTC and may be exploited as a new target for thyroid carcinoma treatment.