USP10/XAB2/ANXA2 axis promotes DNA damage repair to enhance chemoresistance to oxaliplatin in colorectal cancer

作者：Xingwu Liu, shao-Peng Zhang, Yue An, Boyang Xu, Guanyu Yan, Mingjun Sun · 发表于：Journal of experimental & clinical cancer research : CR · 年份：2025 · DOI：10.1186/s13046-025-03357-z · 被引用次数：30 · 研究领域：Medicine

Oxaliplatin-based chemotherapy is the first-line treatment for colorectal cancer (CRC). However, oxaliplatin resistance remains a major challenge contributing to treatment failure and poor prognosis. An increased capacity for DNA damage repair is a key mechanism underlying oxaliplatin resistance. Although XPA binding protein 2 (XAB2) is implicated in various DNA damage repair mechanisms, its specific role in mediating oxaliplatin resistance remains unclear. XAB2 was identified through analysis of public datasets. Western blot analysis and immunohistochemistry were performed to evaluate XAB2 expression, while survival analysis was performed to assess its clinical significance in CRC. Functional experiments were then conducted to assess the impact of XAB2 on proliferation, DNA damage repair, and oxaliplatin resistance in CRC. RNA sequencing (RNA-seq) and Chromatin immunoprecipitation-sequencing (ChIP-seq) were used to identify XAB2 target genes. Co-immunoprecipitation (Co-IP) and mass spectrometry were used to identify the proteins interacting with XAB2. Dual-luciferase reporter assays, ChIP-qPCR, Co-IP, ubiquitination site mass spectrometry, and ubiquitin assays were used to analyse the interactions and potential mechanisms involving XAB2, Annexin A2 (ANXA2), and ubiquitin-specific protease 10 (USP10). XAB2 was found to be expressed in CRC and was associated with poor prognosis in patients with CRC. XAB2 promoted CRC cell proliferation and enhanced oxaliplatin resistance by pr...