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Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8
BACKGROUND: SOX11 is a transcription factor that plays an important role in mantle cell lymphoma development. However, its functional role in head and neck squamous cell carcinoma (HNSCC) remains unknown. METHODS: Protein expression was measured with Western blotting, immunohistochemistry or quantit...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440126/ https://www.ncbi.nlm.nih.gov/pubmed/30922366 http://dx.doi.org/10.1186/s13046-019-1146-7 |
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author | Huang, Junwei Ji, Eoon Hye Zhao, Xinyuan Cui, Li Misuno, Kaori Guo, Mian Huang, Zhigang Chen, Xiaohong Hu, Shen |
author_facet | Huang, Junwei Ji, Eoon Hye Zhao, Xinyuan Cui, Li Misuno, Kaori Guo, Mian Huang, Zhigang Chen, Xiaohong Hu, Shen |
author_sort | Huang, Junwei |
collection | PubMed |
description | BACKGROUND: SOX11 is a transcription factor that plays an important role in mantle cell lymphoma development. However, its functional role in head and neck squamous cell carcinoma (HNSCC) remains unknown. METHODS: Protein expression was measured with Western blotting, immunohistochemistry or quantitative proteomics, and gene expression was measured with quantitative RT-PCR. Functional role of SOX11 in HNSCC was evaluated with MTS/apoptosis, migration, invasion assays and a xenograft model. A SOX11-targeting gene, SDCCAG8, was confirmed with chromatin immunoprecipitation (ChIP), luciferase reporter and rescue assays. RESULTS: SOX11 was up-regulated in recurrent versus primary HNSCC and in highly invasive versus low invasive HNSCC cell lines. Silencing SOX11 in HNSCC cell lines significantly inhibited the cell proliferation, migration, invasion and resistance to Cisplatin, and vice versa. Quantitative proteomic analysis of SOX11-silencing HNSCC cells revealed a number of differentially expressed proteins, including a down-regulated tumor antigen SDCCAG8. Silencing of SDCCAG8 in HNSCC cells also significantly inhibited the cell proliferation, migration and invasion, and vice versa. ChIP assays demonstrated that endogenous SOX11 strongly bound to Sdccag8 gene promoter in highly invasive HNSCC cells. When over-expressed in low invasive HNSCC cells, wild type SOX11 but not mutant SOX11 induced the promoter activity of Sdccag8 and significantly induced the expression of SDCCAG8. However, exogenous mutant SOX11 abolished the expression of SDCCAG8 in highly invasive HNSCC cells. In addition, the inhibitory effects of SOX11 knockdown were partially rescued by over-expression of SDCCAG8 in HNSCC cells. CONCLUSION: Collectively, our findings indicate SOX11 promotes HNSCC progression via the regulation of SDCCAG8. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1146-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6440126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64401262019-04-11 Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 Huang, Junwei Ji, Eoon Hye Zhao, Xinyuan Cui, Li Misuno, Kaori Guo, Mian Huang, Zhigang Chen, Xiaohong Hu, Shen J Exp Clin Cancer Res Research BACKGROUND: SOX11 is a transcription factor that plays an important role in mantle cell lymphoma development. However, its functional role in head and neck squamous cell carcinoma (HNSCC) remains unknown. METHODS: Protein expression was measured with Western blotting, immunohistochemistry or quantitative proteomics, and gene expression was measured with quantitative RT-PCR. Functional role of SOX11 in HNSCC was evaluated with MTS/apoptosis, migration, invasion assays and a xenograft model. A SOX11-targeting gene, SDCCAG8, was confirmed with chromatin immunoprecipitation (ChIP), luciferase reporter and rescue assays. RESULTS: SOX11 was up-regulated in recurrent versus primary HNSCC and in highly invasive versus low invasive HNSCC cell lines. Silencing SOX11 in HNSCC cell lines significantly inhibited the cell proliferation, migration, invasion and resistance to Cisplatin, and vice versa. Quantitative proteomic analysis of SOX11-silencing HNSCC cells revealed a number of differentially expressed proteins, including a down-regulated tumor antigen SDCCAG8. Silencing of SDCCAG8 in HNSCC cells also significantly inhibited the cell proliferation, migration and invasion, and vice versa. ChIP assays demonstrated that endogenous SOX11 strongly bound to Sdccag8 gene promoter in highly invasive HNSCC cells. When over-expressed in low invasive HNSCC cells, wild type SOX11 but not mutant SOX11 induced the promoter activity of Sdccag8 and significantly induced the expression of SDCCAG8. However, exogenous mutant SOX11 abolished the expression of SDCCAG8 in highly invasive HNSCC cells. In addition, the inhibitory effects of SOX11 knockdown were partially rescued by over-expression of SDCCAG8 in HNSCC cells. CONCLUSION: Collectively, our findings indicate SOX11 promotes HNSCC progression via the regulation of SDCCAG8. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1146-7) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-29 /pmc/articles/PMC6440126/ /pubmed/30922366 http://dx.doi.org/10.1186/s13046-019-1146-7 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Huang, Junwei Ji, Eoon Hye Zhao, Xinyuan Cui, Li Misuno, Kaori Guo, Mian Huang, Zhigang Chen, Xiaohong Hu, Shen Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
title | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
title_full | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
title_fullStr | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
title_full_unstemmed | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
title_short | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
title_sort | sox11 promotes head and neck cancer progression via the regulation of sdccag8 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440126/ https://www.ncbi.nlm.nih.gov/pubmed/30922366 http://dx.doi.org/10.1186/s13046-019-1146-7 |
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