SERBP1 is required for efficient HR repair and cisplatin chemoresistance in lung adenocarcinoma.

Resistance to cisplatin limits its clinical efficacy in LUAD patients and leads to poor prognosis. SERPINE1 mRNA binding protein 1 (SERBP1), an RNA-binding protein, is associated with tumorigenesis and progression. However, its specific role in cisplatin resistance and underlying mechanism in LUAD remain unclear. Here, we investigated the hypothesis that SERBP1 drives cisplatin resistance by reinforcing DNA damage repair capacity. We found that SERBP1 was consistently upregulated in cisplatin-resistant LUAD cells compared with cisplatin-sensitive counterparts. Gain-of-function and loss-of-function experiments demonstrated that SERBP1 promoted cisplatin resistance in LUAD. Mechanistically, SERBP1 contributes to cisplatin resistance by stabilizing BRCA1 mRNA, thus activating HR repair mediated by RAD51. Importantly, BRCA1 knockdown attenuated SERBP1-driven cisplatin resistance both in vitro and in vivo, establishing BRCA1 as a critical downstream effector of SERBP1. Collectively, these findings identify SERBP1 as a determinant of cisplatin resistance in LUAD and reveal a SERBP1-BRCA1 axis that promotes HR repair and chemoresistance, thereby highlighting SERBP1 as a potential therapeutic target to overcome cisplatin resistance.