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

作者：Wu Jingjing; Guo Wenzheng; Wen Donghua; Hou Guangyu; Zhou Aiping; Wu Wenjuan^*

来源：Cancer Medicine, 2018, 7(8): 4004-4011.

DOI：10.1002/cam4.1675

• oral squamous cell carcinoma
• programmed cell death ligand 1
• programmed cell death protein 1
• ubiquitin-specific peptidase 9
• X-linked

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-Ll in tumors. Although PD-Ll has been reported to undergo ubiquitination in some cancers, its regulatory mechanisms in oral squamous cell carcinoma (OSCC) arc 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 chromatographymass 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-Ll to induce its deubiquitination and stabilize its protein expression in OSCC. @@@ Conclusion: Our data indicate that USP9X deubiquitinates and stabilizes PD-Ll. Suppressing the expression of USP9X blocks tumor cell growth. The results provide a theoretical basis for USP9X as a therapeutic target.

• 出版日期2018-8
• 单位同济大学; 上海交通大学