miR-9-5p竞争性调节LncRNA SNHG7通过BRAF逆转甲状腺癌碘耐受的机制研究

目前约有10%-15%的分化型甲状腺癌(DTC)在首次131I治疗或首次有效治疗后再次行131I治疗时出现碘耐受（RAIR）。出现RAIR，其疗效将显著下降，故碘耐受机制研究及如何逆转碘耐受成为研究重点及热点。近来研究认为BRAF基因突变在DTC发生机制中起重要作用，而BRAF突变受什么因子调控,目前尚未明确。我们前期研究显示miR-9-5p差异性表达与BRAF可能存在潜在联系，且可作用于下游靶基因BRAF的3端UTR区导致其合成减少。StarBase数据库分析SNHG7与miR-9-5p相关性最密切。我们提出以下假说：miR-9-5p通过竞争性调节LncRNA SNHG7影响BRAF表达，最终起到逆转甲状腺癌碘耐受的作用。本项目拟通过临床组织、细胞及小鼠甲状腺癌模型，研究LncRNA SNHG7及miR-9-5p在甲状腺癌发生发展中的作用，以明确其在甲状腺癌碘耐受及逆转分化方面的机制。

The effectively combined differentiated thyroid cancer treatment is doing radioactive iodine-131 (131I) after subtotal hysterectomy. However, there has been about 10% to 15% of DTC patients experienced radioactive iodine tolerance (RAIR) at first 131I treatment or first effective treatment. In the event of RAIR, the therapeutic effect will decrease significantly. Therefore, its radioactive iodine tolerance mechanism and how to reverse its iodine tolerance has become hot spot of the current research. At present, studies have shown that BRAF gene mutations play an important role in the mechanism of DTC. Yet, there is no relevant research on what regulates mutation of BRAF gene. Our preliminary bioinformatics research showed that the differential expression of miR-9-5p may be associated with BRAF , and it can be applied to the 3-terminal UTR region of downstream target gene BRAF, resulting in a decrease in synthesis, and there is a high prediction in both genes. Further, the StarBase database analysis showed that SNHG7 was most closely related to miR-9-5p.So,we put forward the following hypothesis depending on that the competitive regulation of miR-9-5p on LncRNA SNHG7 does the influence on BRAF reversing thyroid iodine-tolerance .The aim of the study is to investigate the biological behavior of LncRNA SNHG7 and miR-9-5p on thyroid cancer cells through clinical tissues, cells and to establish a model of thyroid cancer in mice.Even more, it will validate the interaction between LncRNA SNHG7 and miR-9-5p, and confirm whether LncRNA SNHG7 & miR-9-5p play an important role in the development of the thyroid cancer animal model or not, which will definite the specific molecular mechanisms of LncRNA SNHG7 and miR-9-5p in thyroid cancer tolerance and reverse the differentiation, in order to provide an objective basis for the experiment in preventing thyroid cancer clinical progress.