Journal
CANCER MANAGEMENT AND RESEARCH
Volume 12, Issue -, Pages 9857-9867Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/CMAR.S270825
Keywords
osteosarcoma; FoxM1; thiostrepton; shRNA; tumorigenesis
Categories
Funding
- National Science Foundation of China [81102041]
- Anhui Provincial Natural Science Foundation [1040606Q17]
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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 FoxMl were also detected in three human OS cell lines (HOS-MNNG, MG-63, and U-20S). 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, FoxMl may serve as a potential therapeutic target for the treatment of OS.
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