In this perspective, we emphasize the current advances and interactions involving the insulin/IGF1R, SIRT1, and FOXOs pathways in the bone and osteosarcoma for a better understanding of the mechanisms potentially underpinning tissue degeneration and tumorigenesis.
Altogether, the results of the current study revealed that high levels of SIRT1 might be a biomarker for a high metastatic rate in patients with osteosarcoma, which suggested that inhibition of SIRT1 might be promising for the therapeutics of osteosarcoma.
The expressions of C2dat1, miR-34a-5p, and Sirt1 in human osteosarcoma cells were altered by transfection with their specific vectors/shRNA or mimic/inhibitor.
Therefore, the present study demonstrated that miR-138 has a role in inhibiting OS cell proliferation and invasion via directly targeting SIRT1, and suggested that the miR-138/SIRT1 axis may become a promising therapeutic target for OS.
We obtained evidence that SIRT1 impairs LKB1 protein stability, and that SIRT1 depletion leads to accumulation of LKB1 in OS cell lines resulting in growth arrest.
Taken together, these findings will shed light on the role and mechanism of miR-133b in regulating osteosarcoma cell growth via the miR-133b/Sirt1 axis, and miR-133b may serve as a potential therapeutic target in osteosarcoma in the future.
Inhibition of OS cell growth and invasion were associated with release of high levels of mature miR-34a from pre-miR-34a prodrug and consequently reduction of protein levels of many miR-34a target genes including SIRT1, BCL2, c-MET, and CDK6.
In summary, high levels of SIRT1 may be a biomarker for a high metastatic rate in osteosarcoma patients; inhibiting SIRT1 could be a potent therapeutic intervention for these patients.
In summary, high levels of SIRT1 may be a biomarker for a high metastatic rate in osteosarcoma patients; inhibiting SIRT1 could be a potent therapeutic intervention for these patients.