长链非编码RNA uc002juh对甲状腺乳头状癌细胞分化和摄碘功能的影响及其机制研究

Dedifferentiation and loss of ability to take up iodide are common phenomenon of papillary thyroid cancer (PTC), which may lead to radioiodine resistance and poor prognosis. Our preliminary study from microarray analysis found that the expression of a long noncoding RNA (lncRNA), uc002juh, was significantly up-regulated in PTC. We further confirmed the findings in larger samples of PTCs. By using bioinformatics analysis, we found that uc002juh can combine the key subunit EZH2 of polycomb repressive complex 2 (PRC2), and there are complementary sequence of uc002juh in the promoter region of several thyroid iodide-metabolizing genes. Based on these findings, we hypothesize that uc002juh may regulate the expression of iodide-metabolizing genes by combining EZH2, and then modulate differentiation and iodine uptake of PTC. We will generate uc002juh knockout cell lines of PTC, and study the effect of uc002juh on differentiation and radioiodine uptake of PTC cells, exploring the underlying mechanisms. The study will help to provide potential therapeutic target for the re-differentiation of PTC.

去分化及摄碘功能缺失是甲状腺乳头状癌发生发展中的常见现象，显著影响患者对放射性碘治疗的反应及其预后。本课题组的前期研究利用长链非编码RNA（lncRNA）芯片发现lncRNA uc002juh在甲状腺乳头状癌中表达明显上调，并扩大样本量得以验证。我们的生物信息学分析结果提示uc002juh能够结合多梳抑制复合体2（PRC2）的关键亚基EZH2，并且多个碘代谢相关基因的启动子区存在与uc002juh互补的序列。由此我们提出假设：uc002juh通过结合EZH2调节碘代谢相关基因的表达，进而影响甲状腺乳头状癌的分化及摄碘功能。本课题拟通过构建uc002juh敲除的甲状腺乳头状癌细胞株，研究uc002juh对甲状腺乳头状癌细胞的分化及摄碘功能的影响，并探讨其可能机制。通过本研究希望为甲状腺乳头状癌的再分化治疗研究提供理论依据和潜在的治疗靶点。