Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells

Objective. Rap1GAP is considered a tumor suppressor gene, but its regulatory mechanism in papillary thyroid cancer (PTC) has not been clearly elucidated. The aim of this study was to explore whether the regulation between Rap1GAP and sodium/iodine transporter (NIS) in tumorigenesis of PTC is mediate...

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Autores principales:	Zheng Yan, Wang Yangyanqiu, Han Shuwen, Mao Jing, Liao Haihong, Chen Gong, Jin Yin, Zhou Qing, Gao Weili
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/316a40c1f0e14e458848e24890e223d6
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spelling	oai:doaj.org-article:316a40c1f0e14e458848e24890e223d62021-11-29T00:55:52ZDownregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells2314-614110.1155/2021/6840642https://doaj.org/article/316a40c1f0e14e458848e24890e223d62021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/6840642https://doaj.org/toc/2314-6141Objective. Rap1GAP is considered a tumor suppressor gene, but its regulatory mechanism in papillary thyroid cancer (PTC) has not been clearly elucidated. The aim of this study was to explore whether the regulation between Rap1GAP and sodium/iodine transporter (NIS) in tumorigenesis of PTC is mediated by TGF-β1. Methods. Western blotting (WB) and quantitative reverse-transcription polymerase chain reaction were performed to analyze the relationships between TGF-β1 concentration and NIS expression. After transfecting BCPAP cells with siRNAs, the Rap1GAP interference model was successfully established. Then, the expression and nuclear localization of TGF-β1 and pathway-related proteins were detected. Flow cytometry was applied to analyze cell apoptosis and cycle. WB was performed to detect apoptotic-related proteins. Wound healing and transwell assays were used to measure cell migration and invasion. EDU was performed to detect cell proliferative activity. Results. The results suggested that TGF-β1 could significantly inhibit the expression of NIS in both mRNA and protein levels. In BCPAP cells transfected with siRNA-Rap1GAP, the expression levels of TGF-β1, Foxp3, and p-Smad3 were significantly increased. By applying immunofluorescence assay, the nuclear localizations of TβR-1 and p-Smad3 were found to be activated. Moreover, anti-TGF-β1 can reverse the decrease in NIS expression caused by downregulation of Rap1GAP. Additionally, the knockdown of Rap1GAP could alter the cell apoptosis, cycle, migration, invasion, and proliferation of BCPAP. Conclusion. The downregulation of Rap1GAP expression can activate the TGF-β/Smad3 pathway to inhibit NIS expression and alter the tumor cell functions of PTC.Zheng YanWang YangyanqiuHan ShuwenMao JingLiao HaihongChen GongJin YinZhou QingGao WeiliHindawi LimitedarticleMedicineRENBioMed Research International, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Zheng Yan Wang Yangyanqiu Han Shuwen Mao Jing Liao Haihong Chen Gong Jin Yin Zhou Qing Gao Weili Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells
description	Objective. Rap1GAP is considered a tumor suppressor gene, but its regulatory mechanism in papillary thyroid cancer (PTC) has not been clearly elucidated. The aim of this study was to explore whether the regulation between Rap1GAP and sodium/iodine transporter (NIS) in tumorigenesis of PTC is mediated by TGF-β1. Methods. Western blotting (WB) and quantitative reverse-transcription polymerase chain reaction were performed to analyze the relationships between TGF-β1 concentration and NIS expression. After transfecting BCPAP cells with siRNAs, the Rap1GAP interference model was successfully established. Then, the expression and nuclear localization of TGF-β1 and pathway-related proteins were detected. Flow cytometry was applied to analyze cell apoptosis and cycle. WB was performed to detect apoptotic-related proteins. Wound healing and transwell assays were used to measure cell migration and invasion. EDU was performed to detect cell proliferative activity. Results. The results suggested that TGF-β1 could significantly inhibit the expression of NIS in both mRNA and protein levels. In BCPAP cells transfected with siRNA-Rap1GAP, the expression levels of TGF-β1, Foxp3, and p-Smad3 were significantly increased. By applying immunofluorescence assay, the nuclear localizations of TβR-1 and p-Smad3 were found to be activated. Moreover, anti-TGF-β1 can reverse the decrease in NIS expression caused by downregulation of Rap1GAP. Additionally, the knockdown of Rap1GAP could alter the cell apoptosis, cycle, migration, invasion, and proliferation of BCPAP. Conclusion. The downregulation of Rap1GAP expression can activate the TGF-β/Smad3 pathway to inhibit NIS expression and alter the tumor cell functions of PTC.
format	article
author	Zheng Yan Wang Yangyanqiu Han Shuwen Mao Jing Liao Haihong Chen Gong Jin Yin Zhou Qing Gao Weili
author_facet	Zheng Yan Wang Yangyanqiu Han Shuwen Mao Jing Liao Haihong Chen Gong Jin Yin Zhou Qing Gao Weili
author_sort	Zheng Yan
title	Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells
title_short	Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells
title_full	Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells
title_fullStr	Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells
title_full_unstemmed	Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells
title_sort	downregulation of rap1gap expression activates the tgf-β/smad3 pathway to inhibit the expression of sodium/iodine transporter in papillary thyroid carcinoma cells
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/316a40c1f0e14e458848e24890e223d6
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Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells

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