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TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma

BACKGROUND: Accumulating evidence shows that autophagy plays a vital role in tumor occurrence, development, and metastasis and even determines tumor prognosis. However, little is known about its role in papillary thyroid carcinoma (PTC) or the potentially oncogenic role of TFE3 in regulating the aut...

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Autores principales: Lu, Hongsheng, Zhu, Chumeng, Ruan, Yanyun, Fan, Lilong, Wei, Kena, Yang, Zhaohui, Chen, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516586/
https://www.ncbi.nlm.nih.gov/pubmed/34660181
http://dx.doi.org/10.1155/2021/3081491
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author Lu, Hongsheng
Zhu, Chumeng
Ruan, Yanyun
Fan, Lilong
Wei, Kena
Yang, Zhaohui
Chen, Qi
author_facet Lu, Hongsheng
Zhu, Chumeng
Ruan, Yanyun
Fan, Lilong
Wei, Kena
Yang, Zhaohui
Chen, Qi
author_sort Lu, Hongsheng
collection PubMed
description BACKGROUND: Accumulating evidence shows that autophagy plays a vital role in tumor occurrence, development, and metastasis and even determines tumor prognosis. However, little is known about its role in papillary thyroid carcinoma (PTC) or the potentially oncogenic role of TFE3 in regulating the autophagy-lysosome system. METHODS: Immunohistochemistry and quantitative real-time PCR (qRT-PCR) were used to examine the expression of TFE3, P62/SQSTM1, and LC3 in PTC and paracancerous tissues. TFE3, P62/SQSTM1, LC3, cathepsin L (CTSL), and cathepsin B (CTSB) were evaluated using Western blot analysis. After inducing TFE3 overexpression by plasmid or TFE3 downregulation by small interfering RNA (siRNA) transfection, MTT, wound healing, and cell migration and invasion assays were used to verify the effects on invasion, migration, and the levels of autophagy-lysosome system-related proteins such as P62/SQSTM1, LC3, CTSL, and CTSB. RESULTS: TFE3 was overexpressed in PTC tissues compared with paracancerous tissues. Analysis of the clinicopathological characteristics of PTC patients showed that high TFE3 expression was significantly correlated with lymph node metastasis. TFE3 overexpression in the PTC cell lines KTC-1 and BCPAP promoted proliferation, invasion, and migration, while TFE3 knockdown had the opposite effects. Furthermore, we identified a positive relationship among the expression levels of TFE3, P62/SQSTM1, LC3, CTSL, and CTSB. We found that silencing TFE3 inhibited the expression of P62/SQSTM1, LC3, CTSL, and CTSB in PTC cells. However, TFE3 overexpression had the opposite effects. CONCLUSIONS: The present study provided evidence for the underlying mechanisms by which TFE3 induces autophagy-lysosome system activity in PTC.
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spelling pubmed-85165862021-10-15 TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma Lu, Hongsheng Zhu, Chumeng Ruan, Yanyun Fan, Lilong Wei, Kena Yang, Zhaohui Chen, Qi Anal Cell Pathol (Amst) Research Article BACKGROUND: Accumulating evidence shows that autophagy plays a vital role in tumor occurrence, development, and metastasis and even determines tumor prognosis. However, little is known about its role in papillary thyroid carcinoma (PTC) or the potentially oncogenic role of TFE3 in regulating the autophagy-lysosome system. METHODS: Immunohistochemistry and quantitative real-time PCR (qRT-PCR) were used to examine the expression of TFE3, P62/SQSTM1, and LC3 in PTC and paracancerous tissues. TFE3, P62/SQSTM1, LC3, cathepsin L (CTSL), and cathepsin B (CTSB) were evaluated using Western blot analysis. After inducing TFE3 overexpression by plasmid or TFE3 downregulation by small interfering RNA (siRNA) transfection, MTT, wound healing, and cell migration and invasion assays were used to verify the effects on invasion, migration, and the levels of autophagy-lysosome system-related proteins such as P62/SQSTM1, LC3, CTSL, and CTSB. RESULTS: TFE3 was overexpressed in PTC tissues compared with paracancerous tissues. Analysis of the clinicopathological characteristics of PTC patients showed that high TFE3 expression was significantly correlated with lymph node metastasis. TFE3 overexpression in the PTC cell lines KTC-1 and BCPAP promoted proliferation, invasion, and migration, while TFE3 knockdown had the opposite effects. Furthermore, we identified a positive relationship among the expression levels of TFE3, P62/SQSTM1, LC3, CTSL, and CTSB. We found that silencing TFE3 inhibited the expression of P62/SQSTM1, LC3, CTSL, and CTSB in PTC cells. However, TFE3 overexpression had the opposite effects. CONCLUSIONS: The present study provided evidence for the underlying mechanisms by which TFE3 induces autophagy-lysosome system activity in PTC. Hindawi 2021-10-07 /pmc/articles/PMC8516586/ /pubmed/34660181 http://dx.doi.org/10.1155/2021/3081491 Text en Copyright © 2021 Hongsheng Lu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lu, Hongsheng
Zhu, Chumeng
Ruan, Yanyun
Fan, Lilong
Wei, Kena
Yang, Zhaohui
Chen, Qi
TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma
title TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma
title_full TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma
title_fullStr TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma
title_full_unstemmed TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma
title_short TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma
title_sort tfe3 regulates the function of the autophagy-lysosome pathway to drive the invasion and metastasis of papillary thyroid carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516586/
https://www.ncbi.nlm.nih.gov/pubmed/34660181
http://dx.doi.org/10.1155/2021/3081491
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