Abstract
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 in vivo 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.
Highlights
Committee of the First Affiliated Hospital of Southern University of Science and Technology, and all the patients signed the written informed consent
Among the predicted miRNAs, miR-34a-5p was selected for examination, and it was downregulated in the TPC-1 and BC-PAP cells when compared to normal thyroid follicular epithelial cells (Figure 5A)
To determine the factors that contribute to the upregulation of Thymidine kinase 1 (TK1) in thyroid carcinoma, the StarBase tool
Summary
Clinical College of Jinan University between 2015 and 2018. Among the subjects, 431 patients were positive for thyroid nodules by ultrasound examination, and 681 patients were negative for thyroid nodules. The thyroid carcinoma at the early stage is commonly curable; patients with advanced thyroid carcinoma have poor prognosis with relatively low 5-years survival rates [3, 4]. High levels of TK1 were correlated with the advanced clinical stage of patients with thyroid carcinoma [11]. Aberrant expression of miRNAs has been reported in various types of cancers including thyroid carcinoma. The thyroid carcinoma cell transfections with these siRNAs or miRNAs were performed using Lipofectamine 2000 reagent (#11668030, Invitrogen, Carlsbad, USA) according to the manufacturer’s protocol, and the transfected cells were collected after 24 h of transfection for further study. The fold change between different groups was determined using comparative Ct method
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