Project description:Purpose:Forkhead box M1 (FOXM1) transcription factor is ubiquitously expressed in embryonic tissues but rare in differentiated cells. Increased expression of FOXM1 is observed in a variety of human malignancies. Here, we sought to characterize the expression and tumorigenic roles of FOXM1 in high-grade serous ovarian carcinoma (HGSOC). Experimental Design:TCGA dataset were analyed to identify potential master transcriptional regulators in HGSOC. Immunohistochemistry was performed to evaluate the clinical significance of FOXM1 in HGSOC. Invasion, clonogenic assays were conducted to determine to functional role of FOXM1. ChIP-seq and luciferase analyses were utilized to identify FOXM1 direct target genes in HGSOC. Association between mutant p53 and FOXM1 expression was investigated through TCGA data analysis, immunohistochemistry stainingand western blot. Results: We identified FOXM1 as a potential key transcription factor in ovarian cancer. FOXM1 was markedly increased in HGSOCs and high FOXM1 expression correlated with poor prognosis in HGSOC patients. Mechanistically, FOXM1 regulated CCNF and KIF20A at transcriptional level through binding on their promoters. Consistently, CCNF and KIF20A were elevated in HGSOCs and correlated with poor prognosis. Importantly, mutant p53 contribute to the high expression of FOXM1 in HGSOCs. Conclusions: These data reveal FOXM1 as a driver oncogenic transcription factor that promotes ovarian cancer malignancy which might be a potential drug target in HGSOC.
Project description:BT-20 breast cancer cells were exposed to a mock transfection, GFP siRNA, or FoxM1 siRNA. Each condition was performed in triplicate, and RNA was collected after 48hrs. Keywords: parallel sample
Project description:FOXM1 plays a key role in M phase in normal cells and is overexpressed in human glioma. We found that FOXM1 deprivation could sensitize the glioma cells to TMZ chemotherapy. To find out the mechanistic regulation of FOXM1 in chemo-resistant genes, we used microarrays to select the potential genes regulated by FOXM1 which dominates in glioma chemo-resistance. U87 glioma cells were transiently transfected with none-target siRNA or FOXM1 siRNA. Total RNA were extracted after 48 hours and subjected to the microarray.
Project description:BT-20 breast cancer cells were exposed to a mock transfection, GFP siRNA, or FoxM1 siRNA. Each condition was performed in triplicate, and RNA was collected after 48hrs.
Project description:Transcription factor FoxM1 is expressed in proliferating cells, and its expression is critical for cell proliferation in embryos and tumors. FoxM1 regulates a multi-gene transcriptional network for cell cycle regulation. We used microarrays to detail the global program of gene expression either directly or indirectly regulated by FoxM1, and distinct classes of up- and down-regulated genes. Experiment Overall Design: Human aortic vascular smooth muscle cells (HAVSMC) were transfected with FoxM1 siRNA and control siRNA for 48 hours. Total RNA was extracted, purified, and prepared for hybridization on Affymetrix microarrays.