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Xia Zhu,1,2 Kangyang Lu,1 Liyu Cao,1,3 Yong Hu,4 Yu Yin,1,3 Yongping Cai1,3 1Department of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei 230032, People’s Republic of China; 2Department of Pathology, Huadong Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, People’s Republic of China; 4Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, People’s Republic of ChinaCorrespondence: Yu Yin; Yongping CaiDepartment of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei 230032, People’s Republic of ChinaEmail aydyinyu@aliyun.com; cyply221@163.comBackground: 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.Keywords: osteosarcoma, FoxM1, thiostrepton, shRNA, tumorigenesis |
