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Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß

SIMPLE SUMMARY: PBDEs have been reported to have endocrine-disrupting and tumour-promoting activity; however, the effects of BDE209 (the highest brominated PBDEs) on the thyroid and the underlying mechanisms are unclear. In this study, we found that long-term exposure to BDE209 could cause chronic t...

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Autores principales: Wang, Xinpei, Cui, Xiujie, Zhao, Qian, Sun, Feifei, Zhao, Ru, Feng, Tingting, Sui, Shaofeng, Han, Bo, Liu, Zhiyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179891/
https://www.ncbi.nlm.nih.gov/pubmed/35681752
http://dx.doi.org/10.3390/cancers14112772
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author Wang, Xinpei
Cui, Xiujie
Zhao, Qian
Sun, Feifei
Zhao, Ru
Feng, Tingting
Sui, Shaofeng
Han, Bo
Liu, Zhiyan
author_facet Wang, Xinpei
Cui, Xiujie
Zhao, Qian
Sun, Feifei
Zhao, Ru
Feng, Tingting
Sui, Shaofeng
Han, Bo
Liu, Zhiyan
author_sort Wang, Xinpei
collection PubMed
description SIMPLE SUMMARY: PBDEs have been reported to have endocrine-disrupting and tumour-promoting activity; however, the effects of BDE209 (the highest brominated PBDEs) on the thyroid and the underlying mechanisms are unclear. In this study, we found that long-term exposure to BDE209 could cause chronic toxicity and potential tumourigenesis by inhibiting the expression and function of TRß, which induces the proliferation of thyroid tissue and the oncogenesis of thyroid carcinoma. These findings emphasize the damaging effects that exposure to BDE209 has on human thyroid and papillary thyroid carcinoma. ABSTRACT: Polybrominated diphenyl ethers (PBDEs) have been reported to possess endocrine-disrupting and tumour-promoting activity. However, the effects of long-term exposure to decabromodiphenyl ether (BDE209) on thyroid tumourigenesis of papillary thyroid carcinoma (PTC) and the underlying mechanisms remain poorly defined. In this study, functional assays in vitro and mouse models in vivo were used to evaluate the toxic effects of long-term exposure to environmental concentrations of BDE209 on the pathogenesis and progression of PTC. MTS, EdU and colony-forming assays confirmed the chronic toxicity of BDE209 on the proliferation of human normal follicular epithelial cell line (Nthy-ori 3-1) and PTC-derived cell lines (TPC-1 and BCPAP). Wound and Transwell assays showed that BDE209 exacerbated the aggressiveness of PTC cells. BDE209 significantly promoted cell proliferation during the S and G2/M phases of the cell cycle. Mechanistically, BDE209 altered the thyroid system by acting as a competitive inhibitor of thyroid receptor beta (TRß) expression and function, which was further proven by public databases and RNA-seq bioinformation analysis. Taken together, these results demonstrated that BDE209 has chronic toxicity and potential tumourigenic effects on the thyroid by inhibiting TRß.
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spelling pubmed-91798912022-06-10 Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß Wang, Xinpei Cui, Xiujie Zhao, Qian Sun, Feifei Zhao, Ru Feng, Tingting Sui, Shaofeng Han, Bo Liu, Zhiyan Cancers (Basel) Article SIMPLE SUMMARY: PBDEs have been reported to have endocrine-disrupting and tumour-promoting activity; however, the effects of BDE209 (the highest brominated PBDEs) on the thyroid and the underlying mechanisms are unclear. In this study, we found that long-term exposure to BDE209 could cause chronic toxicity and potential tumourigenesis by inhibiting the expression and function of TRß, which induces the proliferation of thyroid tissue and the oncogenesis of thyroid carcinoma. These findings emphasize the damaging effects that exposure to BDE209 has on human thyroid and papillary thyroid carcinoma. ABSTRACT: Polybrominated diphenyl ethers (PBDEs) have been reported to possess endocrine-disrupting and tumour-promoting activity. However, the effects of long-term exposure to decabromodiphenyl ether (BDE209) on thyroid tumourigenesis of papillary thyroid carcinoma (PTC) and the underlying mechanisms remain poorly defined. In this study, functional assays in vitro and mouse models in vivo were used to evaluate the toxic effects of long-term exposure to environmental concentrations of BDE209 on the pathogenesis and progression of PTC. MTS, EdU and colony-forming assays confirmed the chronic toxicity of BDE209 on the proliferation of human normal follicular epithelial cell line (Nthy-ori 3-1) and PTC-derived cell lines (TPC-1 and BCPAP). Wound and Transwell assays showed that BDE209 exacerbated the aggressiveness of PTC cells. BDE209 significantly promoted cell proliferation during the S and G2/M phases of the cell cycle. Mechanistically, BDE209 altered the thyroid system by acting as a competitive inhibitor of thyroid receptor beta (TRß) expression and function, which was further proven by public databases and RNA-seq bioinformation analysis. Taken together, these results demonstrated that BDE209 has chronic toxicity and potential tumourigenic effects on the thyroid by inhibiting TRß. MDPI 2022-06-02 /pmc/articles/PMC9179891/ /pubmed/35681752 http://dx.doi.org/10.3390/cancers14112772 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Xinpei
Cui, Xiujie
Zhao, Qian
Sun, Feifei
Zhao, Ru
Feng, Tingting
Sui, Shaofeng
Han, Bo
Liu, Zhiyan
Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß
title Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß
title_full Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß
title_fullStr Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß
title_full_unstemmed Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß
title_short Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß
title_sort long-term exposure to decabromodiphenyl ether promotes the proliferation and tumourigenesis of papillary thyroid carcinoma by inhibiting trß
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179891/
https://www.ncbi.nlm.nih.gov/pubmed/35681752
http://dx.doi.org/10.3390/cancers14112772
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