奥沙利铂是广泛用于结直肠癌（CRC）治疗的一线化疗药物。然而，很大一部分患者往往会对奥沙利铂产生耐药性，导致化疗失败。目前，奥沙利铂耐药性的研究主要集中在癌症进化过程中的遗传和表观遗传改变，而基因组高阶三维（3D）构象的特征仍有待探索。为了研究奥沙利铂耐药过程中染色质构象的变化，我们结合DLO Hi-C、ChIP-seq以及RNA-seq技术对已建立的奥沙利铂耐药细胞系HCT116-OxR以及对照细胞系HCT116。结果表明，19.33%的基因组区域在耐药后发生了A/B区室转化，进一步分析A/B区室转化的基因发现，肿瘤细胞奥沙利铂耐药性的获得与活性氧的减少有关。并增强转移能力。我们的研究基于 DLO Hi-C 和其他表观遗传组学实验揭示了 CRC 细胞和奥沙利铂耐药细胞之间的空间染色质结构差异。更重要的是，我们为奥沙利铂耐药癌症治疗提供了潜在靶点，并提供了一种从 3D 基因组改变的角度研究耐药行为的新方法。© 2023 作者。河南大学和约翰·威利出版的《探索》

Oxaliplatin is a first-line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigenetic alterations during cancer evolution, while the characteristics of high-order three-dimensional (3D) conformation of genome are yet to be explored. In order to investigate the chromatin conformation alteration during oxaliplatin resistance, we performed multi-omics study by combining DLO Hi-C, ChIP-seq as well as RNA-seq technologies on the established oxaliplatin-resistant cell line HCT116-OxR, as well as the control cell line HCT116. The results indicate that 19.33% of the genome regions have A/B compartments transformation after drug resistance, further analysis of the genes converted by A/B compartments reveals that the acquisition of oxaliplatin resistance in tumor cells is related to the reduction of reactive oxygen species and enhanced metastatic capacity. Our research reveals the spatial chromatin structural difference between CRC cells and oxaliplatin resistant cells based on the DLO Hi-C and other epigenetic omics experiments. More importantly, we provide potential targets for oxaliplatin-resistant cancer treatment and a new way to investigate drug resistance behavior under the perspective of 3D genome alteration.© 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.