Poplawski Piotr, Rybicka Beata, Boguslawska Joanna, Rodzik Katarzyna, Visser Theo J, Nauman Alicja, Piekielko-Witkowska Agnieszka
Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813, Warsaw, Poland.
Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.
Mol Cell Endocrinol. 2017 Feb 15;442:58-67. doi: 10.1016/j.mce.2016.12.004. Epub 2016 Dec 8.
Type 1 iodothyronine deiodinase (DIO1) regulates peripheral metabolism of thyroid hormones that control cellular proliferation, differentiation and metabolism. The significance of DIO1 in cancer is unknown. In this study we hypothesized that diminished expression of DIO1, observed in renal cancer, contributes to the carcinogenic process in the kidney. Here, we demonstrate that ectopic expression of DIO1 in renal cancer cells changes the expression of genes controlling cell cycle, including cyclin E1 and E2F5, and results in inhibition of proliferation. The expression of genes encoding collagens (COL1A1, COL4A2, COL5A1), integrins (ITGA4, ITGA5, ITGB3) and transforming growth factor-β-induced (TGFBI) is significantly altered in renal cancer cells with induced expression of DIO1. Finally, we show that overexpression of DIO1 inhibits migration of renal cancer cells. In conclusion, we demonstrate for the first time that loss of DIO1 contributes to renal carcinogenesis and that its induced expression protects cells against cancerous proliferation and migration.
1型碘化甲状腺原氨酸脱碘酶（DIO1）调节甲状腺激素的外周代谢，而甲状腺激素控制细胞增殖、分化和代谢。DIO1在癌症中的意义尚不清楚。在本研究中，我们假设在肾癌中观察到的DIO1表达降低促成了肾脏的致癌过程。在此，我们证明DIO1在肾癌细胞中的异位表达改变了控制细胞周期的基因表达，包括细胞周期蛋白E1和E2F5，并导致增殖受到抑制。在诱导表达DIO1的肾癌细胞中，编码胶原蛋白（COL1A1、COL4A2、COL5A1）、整合素（ITGA4、ITGA5、ITGB3）和转化生长因子-β诱导蛋白（TGFBI）的基因表达发生显著改变。最后，我们表明DIO1的过表达抑制肾癌细胞的迁移。总之，我们首次证明DIO1的缺失促成肾癌发生，其诱导表达可保护细胞免受癌性增殖和迁移。
