<p>FoxM1 is Upregulated in Osteosarcoma and Inhibition of FoxM1 Decreases Osteosarcoma Cell Proliferation, Migration, and Invasion</p>

Abstract

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.

Circ-FOXM1 promotes the proliferation, migration and EMT process of osteosarcoma cells through FOXM1-mediated Wnt pathway activation

“…Repression of Wnt3a/FOXM1/β-Catenin pathway is widely involved in the apoptotic impact of moracin D in breast cancer [ 39 ]. Consistent with the report of Zhu et al [ 18 ], we verified that FOXM1 was expressed at high levels in OS cells. Further, we investigated the regulation of circ-FOXM1 on FOXM1 and found that circ-FOXM1 could positively regulate FOXM1 mRNA expression at post-transcriptional level but not at transcriptional level.…”

“…Circ-FOXM1 (hsa_circ_0025033) is a newly recognized cancer-related circRNA located at chr12: 2966846–2983691 and derived from FOXM1 which has been report to be overexpressed in OS and promotes OS progression [ 18 ]. Presently, circ-FOXM1 has been proven to be upregulated in glioblastoma as screened by circRNA microarray [ 19 ].…”

N6-methyladenosine methyltransferase WTAP-stabilized FOXD2-AS1 promotes the osteosarcoma progression through m6A/FOXM1 axis

“…Previous studies have reported finding that FOXM1 functions as an oncogene in the osteosarcoma [ 19 ]. Thus, in order to investigate the potential regulation mediated by FOXD2-AS1, we tried to explore the interaction within FOXD2-AS1 and FOXM1 mRNA.…”

High-throughput screening for Cushing’s disease: therapeutic potential of thiostrepton via cell cycle regulation

“…FOXM1 plays a crucial role in maintaining cell homeostasis by regulating various biological processes, including proliferation, cell cycle progression, differentiation, DNA damage repair, and angiogenesis (59–61). FOXM1 is involved in cell entry to both the G1/S and G2/M phases by activating genes regulating these checkpoints (62–65). However, our direct comparisons of the TS and Foxm1 KD groups revealed that FOXM1 contributed minimally to the antitumor effects of TS on AtT-20 cells.…”