Similar Datasets
Project description:Forkhead Box R2 (FOXR2) is a forkhead transcription factor located on the X chromosome whose expression is normally restricted to the testis. In this study, we performed a pan-cancer analysis of FOXR2 activation across more than 10,000 adult and pediatric cancer samples and found FOXR2 to be aberrantly upregulated in 70% of all cancer types and 8% of all individual tumors. The majority of tumors (78%) aberrantly express FOXR2 through a previously undescribed epigenetic mechanism that involves hypomethylation of a novel promoter, which was functionally validated as necessary for both FOXR2 expression as well as proliferation in FOXR2-expressing cancer cells. FOXR2 expression is sufficient to enhance tumor formation, and coopts ETS family transcription circuits across cancers. Taken together, this study identifies FOXR2 as potent and ubiquitous oncogene that is epigenetically activated across the majority of human cancers. The identification of ETS transcription circuit hijacking by FOXR2 extends the mechanisms known to activate ETS transcription factors and highlights a mechanism through which transcription factor families cooperate to enhance tumorigenesis.
2022-06-23 | GSE206483 | GEO
Project description:Forkhead Box R2 (FOXR2) is a forkhead transcription factor located on the X chromosome whose expression is normally restricted to the testis. In this study, we performed a pan-cancer analysis of FOXR2 activation across more than 10,000 adult and pediatric cancer samples and found FOXR2 to be aberrantly upregulated in 70% of all cancer types and 8% of all individual tumors. The majority of tumors (78%) aberrantly express FOXR2 through a previously undescribed epigenetic mechanism that involves hypomethylation of a novel promoter, which was functionally validated as necessary for both FOXR2 expression as well as proliferation in FOXR2-expressing cancer cells. FOXR2 expression is sufficient to enhance tumor formation, and coopts ETS family transcription circuits across cancers. Taken together, this study identifies FOXR2 as potent and ubiquitous oncogene that is epigenetically activated across the majority of human cancers. The identification of ETS transcription circuit hijacking by FOXR2 extends the mechanisms known to activate ETS transcription factors and highlights a mechanism through which transcription factor families cooperate to enhance tumorigenesis.
2022-06-23 | GSE206482 | GEO
Project description:Forkhead Box R2 (FOXR2) is a forkhead transcription factor located on the X chromosome whose expression is normally restricted to the testis. In this study, we performed a pan-cancer analysis of FOXR2 activation across more than 10,000 adult and pediatric cancer samples and found FOXR2 to be aberrantly upregulated in 70% of all cancer types and 8% of all individual tumors. The majority of tumors (78%) aberrantly express FOXR2 through a previously undescribed epigenetic mechanism that involves hypomethylation of a novel promoter, which was functionally validated as necessary for both FOXR2 expression as well as proliferation in FOXR2-expressing cancer cells. FOXR2 expression is sufficient to enhance tumor formation, and coopts ETS family transcription circuits across cancers. Taken together, this study identifies FOXR2 as potent and ubiquitous oncogene that is epigenetically activated across the majority of human cancers. The identification of ETS transcription circuit hijacking by FOXR2 extends the mechanisms known to activate ETS transcription factors and highlights a mechanism through which transcription factor families cooperate to enhance tumorigenesis.
2022-06-23 | GSE206481 | GEO
Project description:FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits
| PRJNA851052 | ENA
Project description:FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_IUE_RNAseq]
| PRJNA851053 | ENA
Project description:FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_ChIP]
| PRJNA851061 | ENA
Project description:FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_cells_RNAseq]
| PRJNA851054 | ENA
Project description:Despite significant structural diversity, present evidence suggests that EWS/ETS fusion proteins promote oncogenesis by transcriptionally modulating a common set of target genes. In order to identify these genes, microarray expression analyses were performed on NIH 3T3 polyclonal populations expressing one of three EWS/ETS fusion genes. The majority of these genes can be grouped into seven functional categories, including cellular metabolism and signal transduction. The biologic significance of these target genes was pursued. The effects of modulating genes involved in metabolism were assessed by flux studies and demonstrated shifts in glucose utilization and lactate production as a result of EWS/FLI1 expression. The proto-oncogene coding for serine/threonine kinase PIM3 was found to one of several genes encoding signal transduction proteins that were up-regulated by EWS/ETS fusions. PIM3 was found to be expressed in a panel of human Ewing's family tumor cell lines. Forced expression of PIM3 promoted anchorage-independent growth. Coexpression of a kinase-deficient PIM3 mutant attenuated EWS/FLI1-mediated NIH 3T3 tumorigenesis in immunodeficent mice.
| S-EPMC155223 | biostudies-literature
Project description:The Wnt signalling receptor ROR2 has been identified as a possible therapeutic target in numerous cancers; however, its exact role remains unclear. The aim of this study was to investigate the role of ROR2 in endometrial cancer (EC) and the potential mechanism associated with its altered expression. The association between ROR2 mRNA expression levels and clinicopathological parameters, including overall survival (OS), in EC was analysed in The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) cohort and GEO dataset GSE17025. Four EC cell lines (KLE, MFE-296, Ishikawa and ARK-1) and eight clinical EC samples were analysed for ROR2 methylation via Combined Bisulphite Restriction Analysis (COBRA) and bisulphite genomic sequencing (BGS). In addition, the functional effects of ROR2 overexpression were investigated in Ishikawa and ARK-1 cells following ectopic ROR2 expression. ROR2 promoter methylation or reduced ROR2 expression were both found to correlate with shorter OS, high grade and serous subtype in the TCGA-UCEC and GEO datasets. ROR2 was epigenetically silenced by promoter methylation in both patient samples and cell lines. A significant correlation between ROR2 expression levels and promoter methylation was observed in patient samples (r = -0.797, p = 0.018). ROR2 restoration in ARK-1 significantly decreased invasion ability, with associated changes in epithelial-mesenchymal transition (EMT) markers. ROR2 plays a tumour-suppressor role in EC and is epigenetically suppressed with the development of disease. It may represent a diagnostic or therapeutic candidate for EC.
| S-EPMC7864349 | biostudies-literature
Project description:BACKGROUND:Cancers have long been recognized to be not only genetically but also epigenetically distinct from their tissues of origin. Although genetic alterations underlying oncogene upregulation have been well studied, to what extent epigenetic mechanisms, such as DNA methylation, can also induce oncogene expression remains unknown. RESULTS:Here, through pan-cancer analysis of 4174 genome-wide profiles, including whole-genome bisulfite sequencing data from 30 normal tissues and 35 solid tumors, we discover a strong correlation between gene-body hypermethylation of DNA methylation canyons, defined as broad under-methylated regions, and overexpression of approximately 43% of homeobox genes, many of which are also oncogenes. To gain insights into the cause-and-effect relationship, we use a newly developed dCas9-SunTag-DNMT3A system to methylate genomic sites of interest. The locus-specific hypermethylation of gene-body canyon, but not promoter, of homeobox oncogene DLX1, can directly increase its gene expression. CONCLUSIONS:Our pan-cancer analysis followed by functional validation reveals DNA hypermethylation as a novel epigenetic mechanism for homeobox oncogene upregulation.
| S-EPMC6085761 | biostudies-literature