Thus, our findings identify phospho-AKT in the primary tumor and miR-200c later during tumor progression as prognostic molecules and potential therapeutic targets to prevent progression and metastasis of pediatric osteosarcomas.
We found that hBMSC-MVs promoted U2OS cell proliferation and migration under hypoxia in vitro, and that was partially associated with the PI3K/AKT and HIF-1α pathways.
In conclusion, the study indicated that FER1L4 acted as a tumor suppressor in osteosarcoma via activating PI3K/AKT pathway may be a new prognostic biomarker and potential therapeutic target for osteosarcoma intervention.
We also showed that GCB reduces the phosphorylation of AKT, mTOR and p70S6K and that GCB-induced autophagy in OS can lead to either cell survival or cell death.
Expression levels of miR-206 were significantly decreased in OS tissue specimens, compared to adjacent counterparts, and were inversely correlated with expression of PAX3 and MET mRNA. miR-206 directly interacted with PAX3 and MET mRNA in OS cells. miR-206 overexpression significantly reduced PAX3 and MET gene expression in OS cells <i>in vitro</i>, resulting in significant decreases in Akt1 and Erk1/2 activation, cell proliferation, and metastasis, as well as increases in cell apoptosis, while miR-206 knockdown showed the opposite effects.
PP2A was a direct target of miR-21, which participated in the effects of ASBEL and miR-21 on the activation of phosphatidylinositol 3-kinase/protein kinase 3/glycogen synthase kinase-3β (PI3K/AKT/GSK3β) and mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion.
In addition, the AKT pathway activation promoted TUG1 expression by upregulating the expression of FOXM1, forming a positive feedback loop in osteosarcoma.
LncRNA FER1L4 induces apoptosis and suppresses EMT and the activation of PI3K/AKT pathway in osteosarcoma cells via inhibiting miR-18a-5p to promote SOCS5.
In addition, Western blot showed that metformin activated AMPKα at Tyr172, followed by a downregulated phosphorylation of mammalian target of rapamycin (mTOR)/S6 and feedback activation of p-AKT Ser(473) in both OS MG63 cells and CSCs.
<i>In vivo</i> assays revealed that lnPTENP1 transfection significantly inhibited osteosarcoma tumor growth and significantly increased the protein expression and phosphorylation levels of PI3K and AKT.