CSDE1 enhances genotoxic drug resistance in cancer by modulating RPA2 through CSDE1-eIF3a regulatory complex

• DOI: 10.1016/j.drup.2025.101249
• Publication Date: 2025-05-13T23:14:44Z
• Authors: Jia-Jia Cui; Cheng-Xian Guo; Jun Li; Ao-Xiang Guo; Zhao Zhang; Si-Yu Li; Lei-Yun Wang; Xiang-Bin Jia; Hui Guo; Kun Xia; Zheng-Mao Hu; Qian-Ying Ouyang; Yang Wang; Yu-Ting Xie; Zhao-Qian Liu; Jian-Ting Zhang; Wei Wu; Yong-Heng Chen; Ji-Ye Yin

Genotoxic drug resistance is one of the major obstacles for cancer treatment. Our previous study demonstrates that cold shock domain containing E1 (CSDE1) associated with resistance. In this study, we aim to demonstrate CSDE1 regulates cellular response genotoxic drugs and investigate its mechanism action in Tissues blood samples from patients were used evaluate relationship between response. Comet immunofluorescence assays conducted role DNA damage repair. Systematic knockout mouse models underlying involved. Biotin pull-down, EMSA co-IP probe triplex structure CSDE1-protein (eIF3a)-RNA (RPA2). elevation correlates poor patient increased cell lines drugs. upregulated nucleotide excision repair (NER) homologous recombination (HR) pathways. X-ray irradiation or bleomycin-induced model, systemic resulted damage. both a model lines, inhibited cGAS-STING pathway through RPA2. Mechanistic studies indicated serves as hub binding (RPA2) ternary complex. This reveals new enhancing drugs, detailed zipper-like cross structural CSDE1. It provides strategy sensitivity.