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JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4
BACKGROUND: Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278721/ https://www.ncbi.nlm.nih.gov/pubmed/34261480 http://dx.doi.org/10.1186/s12935-021-02060-1 |
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author | Jing, Chao Liu, Dandan Lai, Qingchuan Li, Linqi Zhou, Mengqian Ye, Beibei Wu, Yue Li, Hong Yue, Kai Wu, Yansheng Duan, Yuansheng Wang, Xudong |
author_facet | Jing, Chao Liu, Dandan Lai, Qingchuan Li, Linqi Zhou, Mengqian Ye, Beibei Wu, Yue Li, Hong Yue, Kai Wu, Yansheng Duan, Yuansheng Wang, Xudong |
author_sort | Jing, Chao |
collection | PubMed |
description | BACKGROUND: Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. RESULTS: The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. CONCLUSIONS: These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC. |
format | Online Article Text |
id | pubmed-8278721 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-82787212021-07-15 JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4 Jing, Chao Liu, Dandan Lai, Qingchuan Li, Linqi Zhou, Mengqian Ye, Beibei Wu, Yue Li, Hong Yue, Kai Wu, Yansheng Duan, Yuansheng Wang, Xudong Cancer Cell Int Primary Research BACKGROUND: Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. RESULTS: The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. CONCLUSIONS: These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC. BioMed Central 2021-07-14 /pmc/articles/PMC8278721/ /pubmed/34261480 http://dx.doi.org/10.1186/s12935-021-02060-1 Text en © The Author(s) 2021 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 | Primary Research Jing, Chao Liu, Dandan Lai, Qingchuan Li, Linqi Zhou, Mengqian Ye, Beibei Wu, Yue Li, Hong Yue, Kai Wu, Yansheng Duan, Yuansheng Wang, Xudong JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4 |
title | JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4 |
title_full | JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4 |
title_fullStr | JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4 |
title_full_unstemmed | JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4 |
title_short | JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4 |
title_sort | josd1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of brd4 |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278721/ https://www.ncbi.nlm.nih.gov/pubmed/34261480 http://dx.doi.org/10.1186/s12935-021-02060-1 |
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