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Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma

BACKGROUND: The immune checkpoint protein programmed cell death ligand 1 (PD‐L1) binds to PD1 to promote tumor cell escape from the killing effect of the immune system. However, there are few studies on the regulatory mechanisms of PD‐L1 in tumors. Although PD‐L1 has been reported to undergo ubiquit...

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Autores principales: Jingjing, Wu, Wenzheng, Guo, Donghua, Wen, Guangyu, Hou, Aiping, Zhou, Wenjuan, Wu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089178/
https://www.ncbi.nlm.nih.gov/pubmed/29992764
http://dx.doi.org/10.1002/cam4.1675
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author Jingjing, Wu
Wenzheng, Guo
Donghua, Wen
Guangyu, Hou
Aiping, Zhou
Wenjuan, Wu
author_facet Jingjing, Wu
Wenzheng, Guo
Donghua, Wen
Guangyu, Hou
Aiping, Zhou
Wenjuan, Wu
author_sort Jingjing, Wu
collection PubMed
description BACKGROUND: The immune checkpoint protein programmed cell death ligand 1 (PD‐L1) binds to PD1 to promote tumor cell escape from the killing effect of the immune system. However, there are few studies on the regulatory mechanisms of PD‐L1 in tumors. Although PD‐L1 has been reported to undergo ubiquitination in some cancers, its regulatory mechanisms in oral squamous cell carcinoma (OSCC) are unclear. Therefore, we aimed to investigate this phenomenon. METHODS: We examined the expression and function of USP9X and PD‐L1 in human oral keratinocytes (HOK) and OSCC cell lines (HN4 and HN30) as the control and relevant cancer cells using western blotting, immunoprecipitation, immunohistochemistry (IHC), T‐cell‐mediated tumor cell killing assay, and liquid chromatography‐mass spectrometry. RESULTS: Programmed cell death ligand 1 was highly expressed in OSCC by the regulation of the ubiquitin‐proteasome pathway. Furthermore, we discovered that ubiquitin‐specific peptidase 9, X‐linked (USP9X) could be combined with PD‐L1 to induce its deubiquitination and stabilize its protein expression in OSCC. CONCLUSION: Our data indicate that USP9X deubiquitinates and stabilizes PD‐L1. Suppressing the expression of USP9X blocks tumor cell growth. The results provide a theoretical basis for USP9X as a therapeutic target.
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spelling pubmed-60891782018-08-17 Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma Jingjing, Wu Wenzheng, Guo Donghua, Wen Guangyu, Hou Aiping, Zhou Wenjuan, Wu Cancer Med Cancer Biology BACKGROUND: The immune checkpoint protein programmed cell death ligand 1 (PD‐L1) binds to PD1 to promote tumor cell escape from the killing effect of the immune system. However, there are few studies on the regulatory mechanisms of PD‐L1 in tumors. Although PD‐L1 has been reported to undergo ubiquitination in some cancers, its regulatory mechanisms in oral squamous cell carcinoma (OSCC) are unclear. Therefore, we aimed to investigate this phenomenon. METHODS: We examined the expression and function of USP9X and PD‐L1 in human oral keratinocytes (HOK) and OSCC cell lines (HN4 and HN30) as the control and relevant cancer cells using western blotting, immunoprecipitation, immunohistochemistry (IHC), T‐cell‐mediated tumor cell killing assay, and liquid chromatography‐mass spectrometry. RESULTS: Programmed cell death ligand 1 was highly expressed in OSCC by the regulation of the ubiquitin‐proteasome pathway. Furthermore, we discovered that ubiquitin‐specific peptidase 9, X‐linked (USP9X) could be combined with PD‐L1 to induce its deubiquitination and stabilize its protein expression in OSCC. CONCLUSION: Our data indicate that USP9X deubiquitinates and stabilizes PD‐L1. Suppressing the expression of USP9X blocks tumor cell growth. The results provide a theoretical basis for USP9X as a therapeutic target. John Wiley and Sons Inc. 2018-07-10 /pmc/articles/PMC6089178/ /pubmed/29992764 http://dx.doi.org/10.1002/cam4.1675 Text en © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Jingjing, Wu
Wenzheng, Guo
Donghua, Wen
Guangyu, Hou
Aiping, Zhou
Wenjuan, Wu
Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma
title Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma
title_full Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma
title_fullStr Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma
title_full_unstemmed Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma
title_short Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma
title_sort deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, x‐linked in oral squamous cell carcinoma
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089178/
https://www.ncbi.nlm.nih.gov/pubmed/29992764
http://dx.doi.org/10.1002/cam4.1675
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