Abstract

Background Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx. Ubiquitin-specific peptidase 31 (USP31) exerts a tumor-promoting role in diverse cancers, but the function of USP31 in NPC is unclear. Methods Relative mRNA and protein levels were detected by qPCR, western blot, and immunohistochemistry. Cell proliferation was measured by cell counting kit and 5-ethynyl-2’-deoxyuridine assays. Ferroptosis was assessed by detecting reactive oxygen species, malondialdehyde, glutathione, and Fe 2+ levels. Radiosensitivity was detected by clonogenic survival and apoptosis analysis. The interaction between USP31 and HOXA10 was estimated by GST pull-down, co-immunoprecipitation, and in vitro deubiquitination assays. The function of USP31 was validated by in vivo tumorigenesis assay. Results Higher levels of USP31 mRNA and protein were detected in NPC samples and cells. USP31 silencing suppressed proliferation, urged ferroptosis, and elevated radiosensitivity of NPC cells. USP31 facilitated HOXA10 protein stability by deubiquitination modification. USP31 down-regulation decreased NPC growth and increased radiosensitivity in vivo . HOXA10 up-regulation reversed USP31 silencing-mediated effects on NPC cell proliferation, ferroptosis, and radiosensitivity. Conclusion USP31 repressed ferroptosis and decreased radiosensitivity of NPC cells by stabilizing HOXA10 protein levels, highlighting that targeting USP31 may be a way for improving the sensitivity of radiotherapy for NPC