Fig. 8. Low expression of USP44 indicates a poor prognosis and is associated with tumour relapse in NPC patients.

a Representative images of immunohistochemical staining for USP44 protein expression is graded according to the intensity of staining in 376 NPC tissues. Scale bars, 50 μm. b Correlations of locoregional recurrence status with the level of USP44 expression detected by IHC. The P value was determined using the two-tailed $\chi$² test. c–e Kaplan–Meier analysis of locoregional recurrence-free survival (c), disease-free survival (d) and overall survival (e) according to the USP44 expression levels. The P values in c–e were determined using the log-rank test. f–h Forest plots of multivariate Cox regression analyses showing the significance of different prognostic variables in NPC locoregional recurrence-free survival (f), disease-free survival (g) and overall survival (h). i Proposed working model of USP44. USP44 recruits and stabilises TRIM25 by removing the K48-linked polyubiquitin chains of TRIM25, and TRIM25 degrades Ku80 by promoting its polyubiquitination and inhibits its recruitment to DSBs, which further inhibits the NHEJ pathway and enhances NPC radiosensitivity. In NPC, hypermethylation of the USP44 promoter leads to its downregulation at the mRNA and protein levels, which blocks the anticancer effect of the USP44-TRIM25-Ku80 axis. Source data are provided as a Source Data file.