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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
by
Guangyu, Hou
, Wenjuan, Wu
, Donghua, Wen
, Aiping, Zhou
, Jingjing, Wu
, Wenzheng, Guo
in
Apoptosis
/ B7-H1 Antigen - genetics
/ B7-H1 Antigen - metabolism
/ Biomarkers
/ Cancer Biology
/ Carcinoma, Squamous Cell - genetics
/ Carcinoma, Squamous Cell - metabolism
/ Cell death
/ Gene Expression
/ Humans
/ Immune checkpoint
/ Keratinocytes - metabolism
/ Ligands
/ Mouth Neoplasms - genetics
/ Mouth Neoplasms - metabolism
/ Oral cancer
/ oral squamous cell carcinoma
/ Original Research
/ PD-1 protein
/ PD-L1 protein
/ programmed cell death ligand 1
/ programmed cell death protein 1
/ Proteasomes
/ Protein Binding
/ Protein Stability
/ Squamous cell carcinoma
/ Ubiquitin Thiolesterase - genetics
/ Ubiquitin Thiolesterase - metabolism
/ Ubiquitination
/ ubiquitin‐specific peptidase 9, X‐linked
2018
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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
by
Guangyu, Hou
, Wenjuan, Wu
, Donghua, Wen
, Aiping, Zhou
, Jingjing, Wu
, Wenzheng, Guo
in
Apoptosis
/ B7-H1 Antigen - genetics
/ B7-H1 Antigen - metabolism
/ Biomarkers
/ Cancer Biology
/ Carcinoma, Squamous Cell - genetics
/ Carcinoma, Squamous Cell - metabolism
/ Cell death
/ Gene Expression
/ Humans
/ Immune checkpoint
/ Keratinocytes - metabolism
/ Ligands
/ Mouth Neoplasms - genetics
/ Mouth Neoplasms - metabolism
/ Oral cancer
/ oral squamous cell carcinoma
/ Original Research
/ PD-1 protein
/ PD-L1 protein
/ programmed cell death ligand 1
/ programmed cell death protein 1
/ Proteasomes
/ Protein Binding
/ Protein Stability
/ Squamous cell carcinoma
/ Ubiquitin Thiolesterase - genetics
/ Ubiquitin Thiolesterase - metabolism
/ Ubiquitination
/ ubiquitin‐specific peptidase 9, X‐linked
2018
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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
by
Guangyu, Hou
, Wenjuan, Wu
, Donghua, Wen
, Aiping, Zhou
, Jingjing, Wu
, Wenzheng, Guo
in
Apoptosis
/ B7-H1 Antigen - genetics
/ B7-H1 Antigen - metabolism
/ Biomarkers
/ Cancer Biology
/ Carcinoma, Squamous Cell - genetics
/ Carcinoma, Squamous Cell - metabolism
/ Cell death
/ Gene Expression
/ Humans
/ Immune checkpoint
/ Keratinocytes - metabolism
/ Ligands
/ Mouth Neoplasms - genetics
/ Mouth Neoplasms - metabolism
/ Oral cancer
/ oral squamous cell carcinoma
/ Original Research
/ PD-1 protein
/ PD-L1 protein
/ programmed cell death ligand 1
/ programmed cell death protein 1
/ Proteasomes
/ Protein Binding
/ Protein Stability
/ Squamous cell carcinoma
/ Ubiquitin Thiolesterase - genetics
/ Ubiquitin Thiolesterase - metabolism
/ Ubiquitination
/ ubiquitin‐specific peptidase 9, X‐linked
2018
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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
Journal Article
Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma
2018
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Overview
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. (i) USP9X and PD‐L1 are highly expressed in OSCC; (ii) USP9X can stabilize PD‐L1 by reducing its ubiquitination in OSCC; (iii) Targeting PD‐L1 through blocking USP9X seems as a promising strategy to treat OSCC.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
/ Carcinoma, Squamous Cell - genetics
/ Carcinoma, Squamous Cell - metabolism
/ Humans
/ Ligands
/ Mouth Neoplasms - metabolism
/ oral squamous cell carcinoma
/ programmed cell death ligand 1
/ programmed cell death protein 1
/ Ubiquitin Thiolesterase - genetics
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