RORC介导小窝蛋白CAV1通过CXC13/CXCR5通路抑制桥本氏甲状腺炎合并乳头状癌的分子机制研究

桥本甲状腺炎合并甲状腺乳头状癌（HT-PTC）比单纯甲状腺乳头状癌（PTC）的恶性程度低，但原因不明。申请人在前期工作中发现HT-PTC中RORC表达上调并且HT-PTC患者预后良好，但其在HT-PTC中的功能及抑癌机制仍不清楚；经转录组芯片筛选我们发现具抑癌作用的CAV1能与RORC相互作用，提示CAV1可能是HT-PTC具良好预后的关键分子。因此本项目将：①评价RORC与CAV1表达改变HT-PTC细胞的基质重塑、血管重建、微环境细胞因子调控等对抑癌功能的影响；②构建RORC及CAV1敲低或过表达后所干涉的信号交流网络并对关键的信号通路进行验证；③利用HT-PTC大样本组织芯片评价关键信号分子与RORC或CAV单独或联合后对HT-PTC预后预测的效果。该课题的开展，期望为HT-PTC的靶向治疗和预后提供潜在干预靶点和预测标志。

Papillary thyroid carcinoma with Hashimoto's thyroiditis with（HT-PTC）is less malignant than Papillary thyroid carcinoma (PTC) only, but the cause of this phenomenon is unknown. In the previous work, the applicant found that RORC expression was up-regulated in HT-PTC and the prognosis of patients with HT-PTC was good, but its function and tumor suppressor mechanism in HT-PTC are still unclear; we screened by transcriptome chip and found that CAV1，a tumor suppression gene, can interact with RORC, suggesting that CAV1 may be a key molecule for good prognosis of HT-PTC. Therefore, this project will: ① Evaluate the effects of RORC and CAV1 expression on the tumor suppressor functions of HT-PTC cells, such as matrix remodeling，vascular reconstruction and Microenvironment cytokine regulation; ② Construct a signal exchange network that interferes with the knockdown or overexpression of RORC and ③ The HT-PTC large sample tissue chip was used to evaluate the effect of key signal molecules and RORC or CAV on the prediction of HT-PTC prognosis. The development of this project is expected to provide potential intervention targets and predictive markers for targeted therapy and prognosis of HT-PTC.