Osteosarcoma (OS) is closely related to the dysregulation of various intracellular signaling pathways, especially the PI3K/Akt signaling pathway. Reportedly, HSP90 was responsible for phospho-Akt stabilization, and both AKT1 and HSP90 were upregulated within osteosarcoma. Herein, we demonstrated that AKT1 and HSP90 mRNA and protein expression were upregulated within osteosarcoma tissues and cells; AKT1 knockdown significantly inhibited OS cell viability. HSP90 knockdown suppressed the phosphorylation of AKT1, decreased ki-67 and Vimentin protein levels, enhanced p21 and E-cadherin protein levels, and inhibited OS cell proliferation and migration; AKT1 overexpression exerted opposing effects and significantly attenuated the effects of HSP90 knockdown. miR-485-5p targeted AKT1 and HSP90 3′-UTR to inhibit AKT1 and HSP90 expression. miR-485-5p overexpression dramatically reduced AKT1, HSP90, and ki-67 proteins, increased E-cadherin protein levels, and inhibited OS cell proliferation and migration. In conclusion, HSP90 knockdown blocked the phosphorylation of AKT1 suppressing the proliferation and migration capacity of OS cells via the PI3K/AKT pathway; miR-485-5p binds to HSP90 and AKT1 in their 3′-UTR to inhibit HSP90 and AKT1 expression, therefore exerting a tumor suppressor function within osteosarcoma.

中文翻译：

---

miR-485-5p / HSP90轴可阻止Akt1磷酸化，从而通过PI3K / AKT途径抑制骨肉瘤细胞的增殖和迁移。

骨肉瘤（OS）与各种细胞内信号通路，特别是PI3K / Akt信号通路的失调密切相关。据报道，HSP90负责磷酸化Akt的稳定，并且骨肉瘤内AKT1和HSP90均被上调。在本文中，我们证明了AKT1和HSP90 mRNA和蛋白表达在骨肉瘤组织和细胞内被上调。AKT1敲低显着抑制OS细胞的生存能力。HSP90基因敲低抑制了AKT1的磷酸化，降低了ki-67和波形蛋白的水平，增强了p21和E-钙粘蛋白的水平，并抑制了OS细胞的增殖和迁移。AKT1过表达发挥相反的作用，并大大减弱了HSP90敲低的作用。miR-485-5p靶向AKT1和HSP90 3'-UTR来抑制AKT1和HSP90的表达。miR-485-5p过表达显着降低了AKT1，HSP90和ki-67蛋白，增加了E-钙粘蛋白蛋白水平，并抑制了OS细胞的增殖和迁移。总之，HSP90敲低阻断了AKT1的磷酸化，从而抑制了OS细胞通过PI3K / AKT途径的增殖和迁移能力。miR-485-5p在其3'-UTR中与HSP90和AKT1结合以抑制HSP90和AKT1的表达，因此在骨肉瘤内发挥肿瘤抑制功能。