Project description:FOXM1 is a vital transcription factor associated with proliferation, expressed extensively and dynamically throughout the cell cycle. Its overexpression in mycosis fungoides correlates with a poor prognosis. However, the specific role of FOXM1 in the pathogenesis of mycosis fungoides remains unclear. In this study, we silenced FOXM1 in the MyLa cell line, which is representative of mycosis fungoides, by transducing it with a lentivirus vector containing shRNA targeting the FOXM1 gene. By comparing MyLa cells transduced with scrambled shRNA as the control, we observed distinct gene expression profiles, notably a decrease in the expression of cell cycle-related genes and an increase in apoptosis-related genes. These changes align with the phenotypic alterations of MyLa cells following FOXM1 silencing.
Project description:FoxM1 is an oncogenic transcription factor that has been linked to the genesis and progression of cancer. FoxM1 not only upregulates cell proliferation and survival genes, but also represses tumor suppressor genes according to our prior study. This ChIP-Seq is a part of our endeveavor to creat a map of the FoxM1 occupied chromatin area in order to better understand the FoxM1 role in tumorigenesis. We present the results of a high-throughput profile of Chromatine alteration in mammalian cells using ChIP-Seq. We developed genome-wide chromatin-state maps of the human HCC cell line Huh7 by extracting approximately 3 billion bases of sequence from chromatin immunoprecipitated DNA in approxiamtoly 33 million reads. We discovered that FoxM1 successfully distinguishes between expressed, stably repressed and poised genes and therefore reflect cell state and lineage potential. This research lays the groundwork for using extensive chromatin profiling to characterize the genes controlled by the oncogeneic transcription factor FoxM1 and their role in the development of FoxM1-induced cancers.
Project description:To study the transcriptional programs of FOXM1 isoforms, we generated a FOXM1 CRISPR knockout cell line then reconstituted it with FOXM1a, b or c and performed RNA sequencing.
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:Purpose:To identify FoxM1-dependent genes and the molecular pathways involved in the regulation of muscle stem cells function, we performed RNA-Sequence of C2C12 from shControl and shFoxM1 cells. Methods: C2C12 mRNA and lncRNA profiles of shControl and shFoxM1 cells (quiescent or activated states) were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000. Results:Using an optimized data analysis workflow, we mapped about 80 million sequence reads per sample to the mouse genome (build mm10) and identified 49,586 transcripts in the control C2C12 and FoxM1-knockdown C2C12 with BWA workflow. Conclusions: Our results represents the first detailed analysis of C2C12 transcriptomes and found that knockdown of FoxM1 perturbed multiple mRNA pathways, as well as for novel lncRNA pathways.