FoxM1 is Upregulated in Osteosarcoma and Inhibition of FoxM1 Decreases Osteosarcoma Cell Proliferation, Migration, and Invasion.

BACKGROUND

Osteosarcoma (OS) is a highly aggressive bone malignancy that is mostly diagnosed in children and young adults. Increasing evidence indicates that the transcription factor Forkhead Box M1 (FoxM1) plays a key role in the pathogenesis of various tumors. However, the function of FoxM1 in OS has not been clearly elucidated.

METHODS

In the present study, we first analyzed the expressions of FoxM1 in human OS and myositis ossificans (MO, included as a control) tissues by immunohistochemistry. To investigate the functional significance of FoxM1 in OS tumorigenesis, we examined the effects of FoxM1 downregulation in MG-63 and HOS-MNNG cells by either short hairpin RNA (shRNA)-mediated gene silencing or treatment with thiostrepton, a specific FoxM1 inhibitor.

RESULTS

FoxM1 was detected in 82.1% (55/67) of OS vs only 10% (2/20) of MO samples. High expressions of FoxM1 were also detected in three human OS cell lines (HOS-MNNG, MG-63, and U-2OS). FoxM1 downregulation significantly reduced MG-63 and HOS-MNNG cell proliferation, migration, and invasion as well as cell cycle arrest in the G2/M phase and increased apoptotic cell death.

CONCLUSION

The present study demonstrated the critical role of FoxM1 in the pathogenesis of OS. Therefore, FoxM1 may serve as a potential therapeutic target for the treatment of OS.