Department of Orthopedic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
The First Affiliated Hospital of Xi'an Medical University, China.
Exp Cell Res. 2020 Sep 15;394(2):112148. doi: 10.1016/j.yexcr.2020.112148. Epub 2020 Jun 23.
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，化疗耐药是 OS 治疗中的一个巨大障碍。然而，OS 化疗耐药的潜在分子机制仍不清楚。在这里，我们报道了对喜树碱（CPT）治疗的耐药性是由 DDX5 的降解驱动的。DDX5 敲低减少了 CPT 处理的 143B 细胞中的细胞死亡和 DNA 损伤，并恢复了细胞增殖。此外，我们发现 DDX5 与 NONO 结合，NONO 是一种 DNA 修复蛋白，并调节 NONO 的功能。我们的数据证实，CPT 诱导的 DDX5 降解后，NONO 的蛋白结合被破坏，这参与了 CPT 的耐药性。总之，根据我们的结果，DDX5 可能是提高 CPT 在 OS 中临床疗效的一个有潜力的治疗靶点。
