Title:USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer
Volume: 20
Issue: 9
关键词:
凋亡,化学抗药性,DUBs,转移,卵巢癌,USP48。
摘要:
Background: Ubiquitin specific protease 48 (USP48) is a member of the deubiquitinating
enzymes (DUBs) family. However, the function of USP48 in ovarian cancer remains unclear.
Objective: The present study reveals that USP48 knockdown could significantly inhibit cell migration
and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation.
Methods: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and
the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous
tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown
significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile,
USP48 deficiency results in the improved survival of mice.
Results: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed
that the high expression of USP48 in ovarian cancer patients is associated with poor survival
and resistance to CBP therapy.
Conclusion: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.