Ubiquitin-specific protease 5 promotes breast cancer progression by stabilizing Forkhead box M1 through deubiquitination

Objective: Breast cancer continues to be a leading and aggressive cancer in women. Despite improvements in early treatment, challenges such as rapid tumor proliferation, metastasis, and drug resistance persist. This research examines how the deubiquitinase ubiquitin-specific protease 5 (USP5) maintains Forkhead box M1 (FOXM1) protein stability and its impact on the advancement of breast cancer. Material and Methods: Data from The Cancer Genome Atlas were utilized to investigate the expression patterns and interactions of USP5 and FOXM1 in breast cancer. The breast cancer cell lines were subjected to functional testing, including invasion, migration, and proliferation. The expression and interaction of USP5 and FOXM1 were examined using quantitative real-time polymerase chain reaction, Western blot, and co-immunoprecipitation analyses. Protein stability and ubiquitination assays were performed to evaluate the effect of USP5 on FOXM1 stability. Results: USP5 stabilized the FOXM1 protein by deubiquitination. Overexpression of USP5 increased FOXM1 levels, while USP5 knockdown accelerated FOXM1 degradation. The deubiquitinating enzyme USP5 inhibited the proteasomal degradation of FOXM1, enhancing its stability. Functional assays showed that USP5 overexpression promoted breast cancer cell progression, while USP5 knockdown inhibited these malignant phenotypes. In vivo analysis showed that FOXM1 knockdown reduced tumor volume, and USP5 overexpression with FOXM1 knockdown increased tumor size. The findings suggest that USP5 promotes breast cancer progression by regulating FOXM1 stability. Conclusion: USP5 enhances breast cancer progression by stabilizing FOXM1 through deubiquitination.