Circular RNA MCM3 recruits USP49 to stabilize PTBP1 and promote cisplatin resistance in cervical squamous cell carcinoma.

Circular RNA MCM3 is upregulated in platinum-resistant cervical squamous cell carcinoma (CSCC) and is associated with poor patient prognosis. However, its role in chemoresistance and the underlying mechanism remain undefined. Here, we demonstrate that circMCM3 drives cisplatin resistance both in vitro and in vivo by enhancing cell proliferation, inhibiting apoptosis and reducing DNA damage. Mechanistically, circMCM3 recruits the deubiquitinase USP49 to stabilize PTBP1, which binds to and stabilizes CCND1 mRNA, thereby facilitating cell cycle transition and reducing DNA damage. Notably, knockdown of PTBP1 or CCND1 abrogates circMCM3-mediated cisplatin resistance, supporting the existence of a functional circMCM3-USP49-PTBP1-CCND1 axis. Collectively, our findings identify circMCM3 as a critical regulator of platinum resistance and suggest that targeting this axis may represent a promising therapeutic strategy for patients with platinum-resistant CSCC.