USP41 Promotes Breast Cancer Via Regulating RACK1

BACKGROUND:Breast cancer (BC) is the most common cancer diagnosed among women and is the second leading cause of cancer death. It is of great significance to explore potential candidate targets for BC.METHODS:The expression of ubiquitin-specific protease 41 (USP41) and its prognosis prediction function was firstly evaluated by TCGA database analysis. Using BC cell lines and specimens from 10 patients with primary BC, the upregulation of USP41 in BC was ensured. By USP41 overexpression or knockdown, its function was studied by cell function assays, small interfering RNA (siRNA), western blot, mass spectrometry, and flow cytometry. The potential mechanism of USP41 was explored via Co-Immunoprecipitation mass spectrometry, and western blot.RESULTS:TCGA database analysis revealed that in metastatic BC, USP41 expression was upregulated and negatively correlated with BC prognosis. In BC cancer cells and cancer specimens, USP41 was also upregulated. Overexpression of USP41 greatly enhanced BC colony-forming ability, proliferation, and migration. In contrast, USP41 knockdown significantly inhibited BC colony-forming ability, proliferation, and migration. Moreover, Co-Immunoprecipitation mass spectrometry results indicated that USP41 could interact with RACK1. USP41 promoted the protein expression of RACK1. The expression of RACK1 in BC tissues was upregulated. Knockdown of RACK1 inhibited cell growth and migration, and reversed the oncogenic function of USP41 in BC cells.CONCLUSIONS:USP41 can be a potential therapeutic target against BC via RACK1.