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...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/6067 |
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| author | Wojciech Gierlikowski Katarzyna Broniarek Łukasz Cheda Zbigniew Rogulski Marta Kotlarek-Łysakowska |
| author_facet | Wojciech Gierlikowski Katarzyna Broniarek Łukasz Cheda Zbigniew Rogulski Marta Kotlarek-Łysakowska |
| author_sort | Wojciech Gierlikowski |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T10:42:45Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:42:45Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-35568e69e86c4d579ab77b031d2ca0002023-11-21T22:48:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012211606710.3390/ijms22116067MiR-181a-5p Regulates NIS Expression in Papillary Thyroid CarcinomaWojciech Gierlikowski0Katarzyna Broniarek1Łukasz Cheda2Zbigniew Rogulski3Marta Kotlarek-Łysakowska4Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, PolandFaculty of Medicine, Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, PolandFaculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, PolandFaculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, PolandWarsaw Genomics, Żwirki i Wigury 101, 02-089 Warsaw, PolandNIS 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.https://www.mdpi.com/1422-0067/22/11/6067NIS<i>SLC5A5</i>microRNAmiR-181a-5ppapillary thyroid carcinomathyroid carcinoma |
| spellingShingle | Wojciech Gierlikowski Katarzyna Broniarek Łukasz Cheda Zbigniew Rogulski Marta Kotlarek-Łysakowska MiR-181a-5p Regulates NIS Expression in Papillary Thyroid Carcinoma International Journal of Molecular Sciences NIS <i>SLC5A5</i> microRNA miR-181a-5p papillary thyroid carcinoma thyroid carcinoma |
| title | MiR-181a-5p Regulates NIS Expression in Papillary Thyroid Carcinoma |
| title_full | MiR-181a-5p Regulates NIS Expression in Papillary Thyroid Carcinoma |
| title_fullStr | MiR-181a-5p Regulates NIS Expression in Papillary Thyroid Carcinoma |
| title_full_unstemmed | MiR-181a-5p Regulates NIS Expression in Papillary Thyroid Carcinoma |
| title_short | MiR-181a-5p Regulates NIS Expression in Papillary Thyroid Carcinoma |
| title_sort | mir 181a 5p regulates nis expression in papillary thyroid carcinoma |
| topic | NIS <i>SLC5A5</i> microRNA miR-181a-5p papillary thyroid carcinoma thyroid carcinoma |
| url | https://www.mdpi.com/1422-0067/22/11/6067 |
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