Liu Chang, Wang Jian, Zhao Li, He Hui, Zhao Pan, Peng Zheng, Liu Feiyuan, Chen Juan, Wu Weiqing, Wang Guangsuo, Dong Fajin
Clinical Medical Research Center, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical College of Jinan University, Shenzhen, China.
Central Lab, Dalian Municipal Central Hospital, Dalian, China.
Front Oncol. 2020 Jan 29;9:1475. doi: 10.3389/fonc.2019.01475. eCollection 2019.
Patients with advanced thyroid carcinoma have poor prognosis with low overall survival. Unfortunately, the underlying mechanisms of thyroid carcinoma progression remain unclear. The elevated expression of thymidine kinase 1 (TK1) has been implicated in the progression of thyroid carcinoma, while the role of TK1 in thyroid carcinoma progression has not been explored. The present study aimed to determine the role TK1 in the progression of thyroid cancer and to explore the underlying molecular mechanisms. In this study, it was found that serum TK1 levels were markedly increased in the patients with thyroid nodules. Further online data mining showed that TK1 expression was upregulated in thyroid carcinoma tissues, and higher expression of TK1 was correlated with shorter disease-free survival of patients with thyroid carcinoma. Silencing of TK1 suppressed cell proliferation, invasion, migration, and epithelial-mesenchymal transition, and also induced cell apoptosis in the thyroid carcinoma cell lines. Animal studies showed that TK1 knockdown inhibited tumor growth of thyroid carcinoma cells. Importantly, miR-34a-5p was found to be downregulated in the thyroid carcinoma cells. Furthermore, miR-34a-5p targeted the 3' untranslated region of TK1 and suppressed the expression of TK1 in thyroid carcinoma cell lines. In summary, first, these results demonstrated the upregulation of TK1 in thyroid nodules and thyroid carcinoma tissues; second, TK1 promoted thyroid carcinoma cell proliferation, invasion, and migration; lastly, TK1 was negatively regulated by miR-34a-5p. Our study may provide novel insights into the role of TK1 in regulating thyroid carcinoma progression.
晚期甲状腺癌患者预后较差，总生存率较低。不幸的是，甲状腺癌进展的潜在机制仍不清楚。胸苷激酶1（TK1）表达升高与甲状腺癌进展有关，而TK1在甲状腺癌进展中的作用尚未得到探索。本研究旨在确定TK1在甲状腺癌进展中的作用，并探索其潜在的分子机制。在本研究中，发现甲状腺结节患者血清TK1水平显著升高。进一步的在线数据挖掘显示，甲状腺癌组织中TK1表达上调，且TK1高表达与甲状腺癌患者较短的无病生存期相关。沉默TK1可抑制甲状腺癌细胞系的细胞增殖、侵袭、迁移和上皮-间质转化，并诱导细胞凋亡。动物研究表明，敲低TK1可抑制甲状腺癌细胞的肿瘤生长。重要的是，发现miR-34a-5p在甲状腺癌细胞中表达下调。此外，miR-34a-5p靶向TK1的3'非翻译区并抑制甲状腺癌细胞系中TK1的表达。总之，首先，这些结果证明了TK1在甲状腺结节和甲状腺癌组织中的上调；其次，TK1促进甲状腺癌细胞的增殖、侵袭和迁移；最后，TK1受miR-34a-5p负调控。我们的研究可能为TK1在调节甲状腺癌进展中的作用提供新的见解。
