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BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma
BACKGROUND: Papillary thyroid carcinoma (PTC) is one of most prevalent malignant endocrine neoplasms, and it is associated with a high frequency of BRAF gene mutations, which lead to lymphatic metastasis and distant metastasis that promote tumor progression. The molecular mechanism of PTC and the ro...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818187/ https://www.ncbi.nlm.nih.gov/pubmed/35123502 http://dx.doi.org/10.1186/s12967-022-03260-7 |
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author | Chen, Xing Lin, Shan Lin, Ying Wu, Songsong Zhuo, Minling Zhang, Ailong Zheng, Junjie You, Zhenhui |
author_facet | Chen, Xing Lin, Shan Lin, Ying Wu, Songsong Zhuo, Minling Zhang, Ailong Zheng, Junjie You, Zhenhui |
author_sort | Chen, Xing |
collection | PubMed |
description | BACKGROUND: Papillary thyroid carcinoma (PTC) is one of most prevalent malignant endocrine neoplasms, and it is associated with a high frequency of BRAF gene mutations, which lead to lymphatic metastasis and distant metastasis that promote tumor progression. The molecular mechanism of PTC and the role of BRAF mutation in PTC progression and development need to be further elucidated. METHODS: In this study, a comprehensive bioinformatics analysis was performed to identify the differentially expressed genes and signaling pathways in thyroid cancer patients carrying mutant BRAF. Then, we confirmed the prognostic role of WT1 in thyroid cancer patients. Immunohistochemistry was performed to measure the expression profile of WT1 in PTC tissue. Lentivirus shWT1 was transfected into BRAF(V600E) (mutant) PTC cells to stably inhibit WT1 expression. CCK-8, EdU, immunofluorescence, colony formation, cell migration, cell wound healing, apoptosis and autophagy assays were performed to assess the biological functions of WT1 in BRAF(V600E) PTC cells. RNA sequencing, immunohistochemistry and immunoblotting were performed to explore the molecular mechanism of WT1 in BRAF(V600E) PTC cells. RESULTS: The results confirmed that “epithelial cell proliferation”, “apoptosis” and “selective autophagy” were closely associated with this BRAF mutant in these thyroid cancer patients. Knocking down BRAF-activated WT1 effectively inhibited the proliferation and migration of BRAF(V600E) PTC cells. Silencing WT1 significantly inhibited autophagy and promoted the apoptosis of BRAF(V600E) PTC cells. Mechanistic investigations showed that silencing WT1 expression remarkably suppressed the AKT/mTOR and ERK/P65 signaling pathways in BRAF(V600E) PTC cells. CONCLUSION: All these results indicate that WT1 is a promising prognostic biomarker and facilitates PTC progression and development of cells carrying the BRAF(V600E) mutation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03260-7. |
format | Online Article Text |
id | pubmed-8818187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88181872022-02-07 BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma Chen, Xing Lin, Shan Lin, Ying Wu, Songsong Zhuo, Minling Zhang, Ailong Zheng, Junjie You, Zhenhui J Transl Med Research BACKGROUND: Papillary thyroid carcinoma (PTC) is one of most prevalent malignant endocrine neoplasms, and it is associated with a high frequency of BRAF gene mutations, which lead to lymphatic metastasis and distant metastasis that promote tumor progression. The molecular mechanism of PTC and the role of BRAF mutation in PTC progression and development need to be further elucidated. METHODS: In this study, a comprehensive bioinformatics analysis was performed to identify the differentially expressed genes and signaling pathways in thyroid cancer patients carrying mutant BRAF. Then, we confirmed the prognostic role of WT1 in thyroid cancer patients. Immunohistochemistry was performed to measure the expression profile of WT1 in PTC tissue. Lentivirus shWT1 was transfected into BRAF(V600E) (mutant) PTC cells to stably inhibit WT1 expression. CCK-8, EdU, immunofluorescence, colony formation, cell migration, cell wound healing, apoptosis and autophagy assays were performed to assess the biological functions of WT1 in BRAF(V600E) PTC cells. RNA sequencing, immunohistochemistry and immunoblotting were performed to explore the molecular mechanism of WT1 in BRAF(V600E) PTC cells. RESULTS: The results confirmed that “epithelial cell proliferation”, “apoptosis” and “selective autophagy” were closely associated with this BRAF mutant in these thyroid cancer patients. Knocking down BRAF-activated WT1 effectively inhibited the proliferation and migration of BRAF(V600E) PTC cells. Silencing WT1 significantly inhibited autophagy and promoted the apoptosis of BRAF(V600E) PTC cells. Mechanistic investigations showed that silencing WT1 expression remarkably suppressed the AKT/mTOR and ERK/P65 signaling pathways in BRAF(V600E) PTC cells. CONCLUSION: All these results indicate that WT1 is a promising prognostic biomarker and facilitates PTC progression and development of cells carrying the BRAF(V600E) mutation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03260-7. BioMed Central 2022-02-05 /pmc/articles/PMC8818187/ /pubmed/35123502 http://dx.doi.org/10.1186/s12967-022-03260-7 Text en © The Author(s) 2022 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chen, Xing Lin, Shan Lin, Ying Wu, Songsong Zhuo, Minling Zhang, Ailong Zheng, Junjie You, Zhenhui BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma |
title | BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma |
title_full | BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma |
title_fullStr | BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma |
title_full_unstemmed | BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma |
title_short | BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma |
title_sort | braf-activated wt1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818187/ https://www.ncbi.nlm.nih.gov/pubmed/35123502 http://dx.doi.org/10.1186/s12967-022-03260-7 |
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