MiR-181a-5p Regulates NIS Expression in Papillary Thyroid Carcinoma
NIS is a potent iodide transporter encoded by the <i>SLC5A5</i> 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 <i>S...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/11/6067 |
| Summary: | NIS is a potent iodide transporter encoded by the <i>SLC5A5</i> 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 <i>SLC5A5</i> 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 <i>SLC5A5</i> 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 <i>SLC5A5</i> 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 <i>SLC5A5</i>, 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 <i>SLC5A5</i>, 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 <i>SLC5A5</i> 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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| ISSN: | 1661-6596 1422-0067 |