Postdoctoral Research Center on Public Health and Preventive Medicine, Xinjiang Medical University, Xinjiang, China.
Fifth Affiliated Hospital, Xinjiang Medical University, Xinjiang, China.
Aging (Albany NY). 2021 Feb 17;13(5):6724-6739. doi: 10.18632/aging.202530.
S-phase kinase-associated protein 2 (Skp2) performs oncogenic functions in cancers; however, how Skp2 is regulated post-transcriptionally is elusive in osteosarcoma. Therefore, we determined whether miR-506 could directly target Skp2 in osteosarcoma to perform its tumor suppressive functions. Here, we found that miR-506 mimics suppressed cell viability, induced apoptosis, and attenuated migration and invasion in osteosarcoma cells. Moreover, upregulation of Skp2 accelerated cell viability and motility and rescued the tumor suppressive effect of miR-506 in osteosarcoma cells. Moreover, downregulation of Skp2 inhibited cell viability and decreased cell motility, which enhanced the antitumor activity induced by miR-506 mimic transfection in osteosarcoma cells. Our western blotting results implied that miR-506 inhibited Skp2 expression and subsequently upregulated Foxo1 and p57 in OS cells. In summary, miR-506 performs an anticancer activity via directly targeting Skp2 in osteosarcoma cells, indicating that inactivation of Skp2 by miR-506 might be an alternative strategy for treating osteosarcoma.
S 期激酶相关蛋白 2（Skp2）在癌症中发挥致癌作用；然而，Skp2 在成骨肉瘤中如何被转录后调控仍不清楚。因此，我们确定 miR-506 是否可以在成骨肉瘤中直接靶向 Skp2 来发挥其肿瘤抑制功能。在这里，我们发现 miR-506 模拟物抑制细胞活力，诱导细胞凋亡，并减弱成骨肉瘤细胞的迁移和侵袭。此外，Skp2 的上调加速了细胞活力和运动，并挽救了 miR-506 在成骨肉瘤细胞中的肿瘤抑制作用。此外，下调 Skp2 抑制细胞活力并降低细胞运动性，从而增强 miR-506 模拟物转染在成骨肉瘤细胞中诱导的抗肿瘤活性。我们的 Western blot 结果表明，miR-506 抑制 Skp2 的表达，随后上调 OS 细胞中的 Foxo1 和 p57。总之，miR-506 通过直接靶向成骨肉瘤细胞中的 Skp2 发挥抗癌活性，表明通过 miR-506 失活 Skp2 可能是治疗成骨肉瘤的一种替代策略。
