USP48 Sustains Chemoresistance And Metastasis In Ovarian Cancer

Ubiquitin specific protease 48(USP48)is a member of the deubiquitinating enzymes(DUBs)family.However,the biological function of USP48 in ovarian cancer remains unclear.Analysis of clinical samples and the TCGA,Kaplan-Meier Plotter database revealed that high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy.Further study revealed that USP48 knockdown significantly inhibits cell migration and invasion in ES2,3AO and A2780 cells,without affecting cell proliferation.After carboplatin(CBP)treatment,the USP48 ablation increased the apoptosis rate,and cleaved PARP and cleaved caspase 3 expression level in ES2,3AO and A2780 cells.Subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly reduced the chemoresistance to CBP,and alleviated the metastasis in vivo.Meanwhile,USP48 deficiency resulted in the improved survival of mice.In summary,USP48 may be a potential therapeutic target for ovarian cancer patients.