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.
Keywords: AKT1; HSP90; Osteosarcoma (OS); PI3K/AKT signaling pathway; miR-485-5p.