{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:37:49Z","timestamp":1760060269906,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre Preludium Grant","doi-asserted-by":"publisher","award":["2015\/17\/N\/NZ2\/01856"],"award-info":[{"award-number":["2015\/17\/N\/NZ2\/01856"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Diamond Grant","award":["2015\/17\/N\/NZ2\/01856"],"award-info":[{"award-number":["2015\/17\/N\/NZ2\/01856"]}]},{"name":"Medical University of Warsaw","award":["2015\/17\/N\/NZ2\/01856"],"award-info":[{"award-number":["2015\/17\/N\/NZ2\/01856"]}]},{"name":"Postgraduate School of Molecular Medicine","award":["2015\/17\/N\/NZ2\/01856"],"award-info":[{"award-number":["2015\/17\/N\/NZ2\/01856"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>SLC5A8 is a protein coded by the SLC5A8 gene, and has been proposed as a tumor suppressor and iodide transporter. Its expression is reduced in papillary thyroid carcinoma (PTC), yet the mechanisms underlying this phenomenon are largely unknown. We hypothesized that SLC5A8 expression in PTC is reduced by microRNAs and can be modulated by their inhibition. We used real-time PCR to analyze the expression of SLC5A8 and the microRNAs of interest in a set of 49 PTC\/normal tissue pairs. We used an in silico approach to identify microRNAs upregulated in PTC and putatively binding to the SLC5A8 transcript. Luciferase assays were performed to confirm the direct binding of synthetic microRNAs to the 3\u2032UTR of SLC5A8. Subsequently, using mir-expressing plasmids and microRNA sponges, including a microRNA sponge designed to simultaneously inhibit three selected microRNAs, we checked the impact of the modulation of microRNAs on endogenous SLC5A8. Finally, we investigated if modulation of SLC5A8 induces changes in transcriptomes. We confirmed the downregulation of SLC5A8 in PTC. In silico analysis revealed microRNAs potentially targeting SLC5A8. Luciferase assay confirmed direct binding between the 3\u2032UTR of SLC5A8 and miR-181a-5p, miR-182-5p, and miR-494-3p. MiR-181a-5p and miR-182-5p were upregulated in PTC. In HEK293 cell lines, transfection with mir-181a- and mir-182-expressing plasmids decreased endogenous SLC5A8 mRNA, while silencing of miR-181a-5p, miR-182-5p, miR-494-3p, and all three microRNAs simultaneously increased SLC5A8 expression; however, only simultaneous inhibition was able to induce changes visible for SLC5A8 protein. Changes in SLC5A8 expression did not alter the whole transcriptome significantly. This study shows microRNA-dependent regulation of SLC5A8 expression and underlines the potential effectiveness of simultaneous inhibition of a few microRNAs to derepress their common target.<\/jats:p>","DOI":"10.3390\/ijms26167889","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T16:09:55Z","timestamp":1755274195000},"page":"7889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MicroRNAs and Their Inhibition in Modulating SLC5A8 Expression in the Context of Papillary Thyroid Carcinoma"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1706-4436","authenticated-orcid":false,"given":"Wojciech","family":"Gierlikowski","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland"},{"name":"Department of Genomic Medicine, Medical University of Warsaw, Nielubowicza 5, 02-097 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jowita","family":"Grz\u0119dzicka","sequence":"additional","affiliation":[{"name":"Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Konieczek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical University of Warsaw, \u017bwirki i Wigury 63A, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-1253","authenticated-orcid":false,"given":"Marta","family":"Kotlarek-\u0141ysakowska","sequence":"additional","affiliation":[{"name":"Warsaw Genomics, \u017bwirki i Wigury 101, 02-089 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1042\/BST0330237","article-title":"Biological functions of SLC5A8, a candidate tumour suppressor","volume":"33","author":"Ganapathy","year":"2005","journal-title":"Biochem. 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