ABSTRACT
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.
Subject(s)
B7-H1 Antigen/metabolism , Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/metabolism , Ubiquitin Thiolesterase/metabolism , B7-H1 Antigen/genetics , Biomarkers , Carcinoma, Squamous Cell/genetics , Gene Expression , Humans , Keratinocytes/metabolism , Mouth Neoplasms/genetics , Protein Binding , Protein Stability , Ubiquitin Thiolesterase/genetics , UbiquitinationABSTRACT
The aim of this study was to prospectively evaluate and compare the effects of radiofrequency thermocoagulation of the first division branches of the trigeminal nerve (trigeminal peripheral division radiofrequency thermocoagulation, PRT) versus conventional radiofrequency (CRF) in the treatment of first division idiopathic trigeminal neuralgia (ITN). Fifty patients with first division ITN were randomly divided into two groups. The 20 patients in group 1 were treated with CRF, while the remaining 30 patients in group 2 were treated using PRT. The immediate therapeutic effects, side effects and recurrence rate of idiopathic trigeminal neuralgia were evaluated. The immediate efficacy rates were 95% and 93% in groups 1 and 2, respectively. The recurrence rates of ITN at the 3-year follow-up were 25% and 27% for group 1 and group 2, respectively, and 35% and 40%, respectively, 5 years after treatment. There were no significant differences between groups 1 and 2 at any time. Our study demonstrates that PRT is an effective way to treat first division ITN.
