Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Unfortunately, chemo-resistance is a huge obstacle in the treatment of OS. However, the underlying molecular mechanisms of OS chemo-resistance still remain unknown. Here we reported that the resistance to camptothecin (cpt) therapy was driven by degradation of DDX5. DDX5 knockdown decreased cell death and DNA damage and recovered cell proliferation in cpt treated 143B cells. Furthermore, we found that DDX5 bound to NONO, a kind of DNA repairing protein, and regulated NONO functions. Our data verified that cpt-induced degradation of DDX5 following by breaking down the protein bound of NONO, which participated in the resistance of cpt. In the summary, according to our results, DDX5 might be a potential therapeutic target for improving clinical outcomes of cpt in OS.

骨肉瘤（OS）是儿童和青少年中最常见的原发性恶性骨肿瘤。不幸的是，耐化学性是OS治疗的巨大障碍。但是，OS化学抗性的潜在分子机制仍然未知。在这里，我们报道了喜树碱（cpt）治疗的耐药性是由DDX5降解引起的。DDX5敲低可降低cpt处理的143B细胞的细胞死亡和DNA损伤并恢复细胞增殖。此外，我们发现DDX5与NONO（一种DNA修复蛋白）结合，并调节NONO功能。我们的数据验证了cpt诱导的DDX5降解是通过破坏参与cpt抗性的NONO的蛋白结合而实现的。在总结中，根据我们的结果，