Forkhead box M1 (FOXM1) transcription factor is a key oncogenic driver of aggressive human meningioma progression

Abstract

2020) Neuropathology and Applied Neurobiology 46, 125-141 Forkhead box M1 (FOXM1) transcription factor is a key oncogenic driver of aggressive human meningioma progression Aims: Aggressive meningioma remains incurable with neither chemo-nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression. Methods: Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression-free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked-down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM-Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)-pretreated or control IOMM-Lee cells were implanted subcutaneously in nude mice. Results: FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of b-catenin, cyclin D1, p21, interleukin-8, vascular endothelial growth factor-A, PLAU, and epithelial-to-mesenchymal transition-related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model. Conclusions: Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.

Identification of Crucial Genes Associated With Immune Cell Infiltration in Hepatocellular Carcinoma by Weighted Gene Co-expression Network Analysis

“…BIRC5 also promotes cell proliferation and invasion and inhibits apoptosis and cycle arrest (Su, 2016), and the aberrant methylation of BIRC5 was consistent basically with the previous report, which was identified by bioinformatics analysis (Cai et al, 2019). FOXM1 contributes to multiple cancers by promoting cellular proliferation and tumor initiation via β-catenin and cyclin D1 (Kim et al, 2019;Shukla et al, 2019). Bioinformatics analysis showed that FOXM1 was also involved in the development of hepatitis B virus (HBV)-related HCC (Xie et al, 2019).…”

<p>CCNB1 Expedites the Progression of Cervical Squamous Cell Carcinoma via the Regulation by FOXM1</p>

“…Knockdown of FOXM1 in malignant meningioma cells led to decreased cell proliferation, angiogenesis and invasion by regulating cyclin D1 and p21. 27 While our Western blot results exhibited that siCCNB1 expedited the p53 pathway, while further oe-FOXM1 or CTPB contributed to the p53 pathway deficit.…”

FoxM1 promotes Wnt/β‐catenin pathway activation and renal fibrosis via transcriptionally regulating multi‐Wnts expressions

“…However, the increase in Wnts expressions induced by overexpression of FoxM1 in cultured renal tubular epithelial cells were not completely match what observed in UUO kidneys, which suggested that other factors other than FoxM1 might be involved in regulating Wnts expression. Moreover, FoxM1 was able to regulate β‐catenin transcription 27,28 and facilitate β‐catenin nuclear translocation 29‐31 . These studies indicated that the effect of FoxM1 in promoting renal fibrosis may not completely rely on regulating Wnts expressions.…”