MiR-181a-5p Regulates NIS Expression in Papillary Thyroid Carcinoma |
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Authors: | Wojciech Gierlikowski,Katarzyna Broniarek, ukasz Cheda,Zbigniew Rogulski,Marta Kotlarek- ysakowska |
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Affiliation: | 1.Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland;2.Faculty of Medicine, Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland;3.Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland; (Ł.C.); (Z.R.);4.Warsaw Genomics, Żwirki i Wigury 101, 02-089 Warsaw, Poland; |
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Abstract: | NIS is a potent iodide transporter encoded by the SLC5A5 gene. Its expression is reduced in papillary thyroid carcinoma (PTC). In this study we analyzed the impact of miR-181a-5p on NIS expression in the context of PTC. We used real-time PCR to analyze the expression of SLC5A5 and miR-181a-5p in 49 PTC/normal tissue pairs. Luciferase assays and mutagenesis were performed to confirm direct binding of miR-181a-5p to the 3′UTR of SLC5A5 and identify the binding site. The impact of modulation of miR-181a-5p using appropriate plasmids on endogenous NIS and radioactive iodine accumulation was verified. We confirmed downregulation of SLC5A5 and concomitant upregulation of miR-181a-5p in PTC. Broadly used algorithms did not predict the binding site of miR-181a-5p in 3′UTR of SLC5A5, but we identified and confirmed the binding site through mutagenesis using luciferase assays. In MCF7 and HEK293-flhNIS cell lines, transfection with mir-181a-expressing plasmid decreased endogenous SLC5A5, whereas silencing of miR-181a-5p increased it. We observed similar tendencies in protein expression and radioactive iodine accumulation. This study shows for the first time that miR-181a-5p directly regulates SLC5A5 expression in the context of PTC and may decrease efficacy of radioiodine treatment. Accordingly, miR-181a-5p may serve as an emerging target to enhance the efficacy of radioactive iodine therapy. |
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Keywords: | NIS SLC5A5 microRNA miR-181a-5p papillary thyroid carcinoma thyroid carcinoma PTC |
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