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The role of miR-139-5p in radioiodine-resistant thyroid cancer

PURPOSE: Radioiodine I-131 (RAI) is the therapy of choice for differentiated thyroid cancer (DTC). Between 5% and 15% of DTC patients become RAI refractory, due to the loss of expression/function of iodide metabolism components, especially the Na/I symporter (NIS). We searched for a miRNA profile as...

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Autores principales: Pecce, V., Sponziello, M., Verrienti, A., Grani, G., Abballe, L., Bini, S., Annunziata, S., Perotti, G., Salvatori, M., Zagaria, L., Maggisano, V., Russo, D., Filetti, S., Durante, C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514163/
https://www.ncbi.nlm.nih.gov/pubmed/36933170
http://dx.doi.org/10.1007/s40618-023-02059-7
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author Pecce, V.
Sponziello, M.
Verrienti, A.
Grani, G.
Abballe, L.
Bini, S.
Annunziata, S.
Perotti, G.
Salvatori, M.
Zagaria, L.
Maggisano, V.
Russo, D.
Filetti, S.
Durante, C.
author_facet Pecce, V.
Sponziello, M.
Verrienti, A.
Grani, G.
Abballe, L.
Bini, S.
Annunziata, S.
Perotti, G.
Salvatori, M.
Zagaria, L.
Maggisano, V.
Russo, D.
Filetti, S.
Durante, C.
author_sort Pecce, V.
collection PubMed
description PURPOSE: Radioiodine I-131 (RAI) is the therapy of choice for differentiated thyroid cancer (DTC). Between 5% and 15% of DTC patients become RAI refractory, due to the loss of expression/function of iodide metabolism components, especially the Na/I symporter (NIS). We searched for a miRNA profile associated with RAI-refractory DTC to identify novel biomarkers that could be potential targets for redifferentiation therapy. METHODS: We analyzed the expression of 754 miRNAs in 26 DTC tissues: 12 responsive (R) and 14 non-responsive (NR) to RAI therapy. We identified 15 dysregulated miRNAs: 14 were upregulated, while only one (miR-139-5p) was downregulated in NR vs. R tumors. We investigated the role of miR-139-5p in iodine uptake metabolism. We overexpressed miR-139-5p in two primary and five immortalized thyroid cancer cell lines, and we analyzed the transcript and protein levels of NIS and its activation through iodine uptake assay and subcellular protein localization. RESULTS: The finding of higher intracellular iodine levels and increased cell membrane protein localization in miR-139-5p overexpressing cells supports the role of this miRNA in the regulation of NIS function. CONCLUSIONS: Our study provides evidence of miR-139-5p involvement in iodine uptake metabolism and suggests its possible role as a therapeutic target in restoring iodine uptake in RAI-refractory DTC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40618-023-02059-7.
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spelling pubmed-105141632023-09-23 The role of miR-139-5p in radioiodine-resistant thyroid cancer Pecce, V. Sponziello, M. Verrienti, A. Grani, G. Abballe, L. Bini, S. Annunziata, S. Perotti, G. Salvatori, M. Zagaria, L. Maggisano, V. Russo, D. Filetti, S. Durante, C. J Endocrinol Invest Original Article PURPOSE: Radioiodine I-131 (RAI) is the therapy of choice for differentiated thyroid cancer (DTC). Between 5% and 15% of DTC patients become RAI refractory, due to the loss of expression/function of iodide metabolism components, especially the Na/I symporter (NIS). We searched for a miRNA profile associated with RAI-refractory DTC to identify novel biomarkers that could be potential targets for redifferentiation therapy. METHODS: We analyzed the expression of 754 miRNAs in 26 DTC tissues: 12 responsive (R) and 14 non-responsive (NR) to RAI therapy. We identified 15 dysregulated miRNAs: 14 were upregulated, while only one (miR-139-5p) was downregulated in NR vs. R tumors. We investigated the role of miR-139-5p in iodine uptake metabolism. We overexpressed miR-139-5p in two primary and five immortalized thyroid cancer cell lines, and we analyzed the transcript and protein levels of NIS and its activation through iodine uptake assay and subcellular protein localization. RESULTS: The finding of higher intracellular iodine levels and increased cell membrane protein localization in miR-139-5p overexpressing cells supports the role of this miRNA in the regulation of NIS function. CONCLUSIONS: Our study provides evidence of miR-139-5p involvement in iodine uptake metabolism and suggests its possible role as a therapeutic target in restoring iodine uptake in RAI-refractory DTC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40618-023-02059-7. Springer International Publishing 2023-03-18 2023 /pmc/articles/PMC10514163/ /pubmed/36933170 http://dx.doi.org/10.1007/s40618-023-02059-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Pecce, V.
Sponziello, M.
Verrienti, A.
Grani, G.
Abballe, L.
Bini, S.
Annunziata, S.
Perotti, G.
Salvatori, M.
Zagaria, L.
Maggisano, V.
Russo, D.
Filetti, S.
Durante, C.
The role of miR-139-5p in radioiodine-resistant thyroid cancer
title The role of miR-139-5p in radioiodine-resistant thyroid cancer
title_full The role of miR-139-5p in radioiodine-resistant thyroid cancer
title_fullStr The role of miR-139-5p in radioiodine-resistant thyroid cancer
title_full_unstemmed The role of miR-139-5p in radioiodine-resistant thyroid cancer
title_short The role of miR-139-5p in radioiodine-resistant thyroid cancer
title_sort role of mir-139-5p in radioiodine-resistant thyroid cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514163/
https://www.ncbi.nlm.nih.gov/pubmed/36933170
http://dx.doi.org/10.1007/s40618-023-02059-7
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