a Department of Orthopaedics , The First Affiliated Hospital , China Medical University , Shenyang , Liaoning Province , PR China.
Cell Cycle. 2018;17(1):43-52. doi: 10.1080/15384101.2017.1387700. Epub 2017 Dec 22.
Cdc20 (cell division cycle 20 homologue) has been reported to exhibit an oncogenic role in human tumorigenesis. However, the function of Cdc20 in osteosarcoma (OS) has not been investigated. In the current study, we aim to explore the role of Cdc20 in human OS cells. Multiple approaches were used to measure cell growth, apoptosis, cell cycle, migration and invasion in OS cells after depletion of Cdc20 or overexpression of Cdc20. We found that down-regulation of Cdc20 inhibited cell growth, induced apoptosis and triggered cell cycle arrest in OS cells. Moreover, Cdc20 down-regulation let to inhibition of cell migration and invasion in OS cells. Consistently, overexpression of Cdc20 in OS cells promoted cell growth, inhibited apoptosis, enhanced cell migration and invasion. Mechanistically, our Western blotting results showed that overexpression of Cdc20 reduced the expression of Bim and p21, whereas depletion of Cdc20 upregulated Bim and p21 levels in OS cells. Altogether, our findings demonstrated that Cdc20 exerts its oncogenic role partly due to regulation of Bim and p21 in OS cells, suggesting that targeting Cdc20 could be useful for the treatment of OS.
Cdc20(细胞分裂周期 20 同源物)已被报道在人类肿瘤发生中具有致癌作用。然而,Cdc20 在骨肉瘤(OS)中的功能尚未得到研究。在本研究中,我们旨在探讨 Cdc20 在人骨肉瘤细胞中的作用。采用多种方法检测 Cdc20 耗竭或过表达后 OS 细胞的细胞生长、凋亡、细胞周期、迁移和侵袭。我们发现下调 Cdc20 抑制 OS 细胞的生长,诱导细胞凋亡并引发细胞周期停滞。此外,Cdc20 下调抑制 OS 细胞的迁移和侵袭。一致地,Cdc20 在 OS 细胞中的过表达促进细胞生长,抑制细胞凋亡,增强细胞迁移和侵袭。机制上,我们的 Western blot 结果表明,Cdc20 的过表达降低了 Bim 和 p21 的表达,而 Cdc20 的耗竭则上调了 OS 细胞中 Bim 和 p21 的水平。总之,我们的研究结果表明,Cdc20 在 OS 细胞中发挥其致癌作用部分是由于对 Bim 和 p21 的调节,表明靶向 Cdc20 可能对 OS 的治疗有用。