USP5 promotes glycolysis in cervical cancer by stabilizing FOXM1

Cervical cancer treatment faces challenges like limited efficacy, side effects, and high costs. Hence, unearthing feasible objectives targeting pathogeny is compulsory for the management of cervical cancer. Ubiquitin-specific peptidase 5 (USP5) acts as an oncogene in various cancers, but its role in cervical cancer continues vague. USP5 expression was assessed bioinformatically and experimentally. Studies involving gain and loss of function were performed in Hela and CaSki cells as well as in a xenograft mouse model. Assays included reverse transcription-quantitative polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8), clonogenesis, flow cytometry, western blot, co-immunoprecipitation (Co-IP), and immunohistochemistry. High USP5 expression predicted poor prognosis in cervical cancer patients. USP5 knockdown inhibited cell proliferation, glycolysis (reducing GLUT1, PGC-1α, HK, LDHA expression, glucose uptake, and lactate production), and induced apoptosis, while overexpression had opposite effects. USP5 stabilized FOXM1 via deubiquitination, which was crucial for USP5-mediated oncogenic effects. In vivo, USP5 silencing suppressed tumor growth and glycolytic gene expression. USP5 promoted cervical cancer progression by enhancing proliferation and glycolysis and suppressing apoptosis through deubiquitination and stabilization of FOXM1, identifying it as a potential therapeutic target.