The USP19-DnaJC7 Axis Stabilizes p53 in Cisplatin-Treated Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) poses a challenge owing to its high rate of recurrence and drug resistance, resulting in a 5-year survival rate of 30% in advanced stages. To elucidate the molecular mechanisms underlying EOC recurrence, we analyzed transcriptome data from patients with EOC and identified elevated USP19, a deubiquitinating enzyme, as being elevated in patients without recurrence in our previous study. Single-cell RNA sequencing analysis revealed that increased USP19 expression in epithelial cells is associated with activation of apoptotic pathways, suggesting that USP19 may inhibit EOC recurrence through deubiquitination of its binding proteins. Using the protein-protein interaction database, we identified DnaJC7 as a binding partner of USP19 and confirmed their interaction experimentally. USP19-mediated deubiquitination of DnaJC7 increases its protein stability. Notably, upregulation of USP19 and DnaJC7 disrupted the interaction between p53 and MDM2, and knockdown of USP19 and DnaJC7 resulted in decreased p53 expression following cisplatin treatment. These findings highlight the therapeutic potential of enhancing the USP19-DnaJC7 axis to stabilize p53 and improve cisplatin efficacy. Promoting USP19-mediated deubiquitination by stabilizing DnaJC7 may offer a novel combination strategy to enhance the efficacy of cisplatin-based cancer therapy.