Open AccessDeubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma
Author(s) -
Jingjing Wu,
Wenzheng Guo,
Donghua Wen,
Guangyu Hou,
Aiping Zhou,
Wenjuan Wu
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1675
Subject(s) - cancer research , immunoprecipitation , ubiquitin , programmed cell death , immunohistochemistry , cell , cell growth , biology , proteasome , apoptosis , blot , cancer , chemistry , microbiology and biotechnology , antibody , immunology , biochemistry , gene , genetics
Background The immune checkpoint protein programmed cell death ligand 1 ( PD ‐L1) binds to PD 1 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 USP 9X and PD ‐L1 in human oral keratinocytes ( HOK ) and OSCC cell lines ( HN 4 and HN 30) 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 ( USP 9X) could be combined with PD ‐L1 to induce its deubiquitination and stabilize its protein expression in OSCC . Conclusion Our data indicate that USP 9X deubiquitinates and stabilizes PD ‐L1. Suppressing the expression of USP 9X blocks tumor cell growth. The results provide a theoretical basis for USP 9X as a therapeutic target.