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FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_ChIP]

ABSTRACT: FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_ChIP]

PROVIDER: PRJNA851061 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19754300_1.fastq.gz	Fastqsanger.gz
	SRR19754300_2.fastq.gz	Fastqsanger.gz
	SRR19754301_1.fastq.gz	Fastqsanger.gz
	SRR19754301_2.fastq.gz	Fastqsanger.gz
	SRR19754302_1.fastq.gz	Fastqsanger.gz

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FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_IUE_RNAseq]

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.

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FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_cells_RNAseq]

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FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits

Project description:FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits

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Project description:FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_IUE_RNAseq]

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FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_cells_RNAseq]

Project description:FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits [FOXR2_cells_RNAseq]

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FOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits

Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated [Multiome]

Project description:The transcription factor FOXR2 is the universal driver of childhood central nervous system neuroblastoma, FOXR2 activated (NB-FOXR2). NB-FOXR2 tumors arise exclusively in the brain hemispheres, and despite morphological similarities to other pediatric brain tumors, they are a molecularly distinct entity based on DNA methylation profiling. The cell-of-origin is unknown. Here, we profiled a cohort of rare NB-FOXR2 tumors by bulk and single-cell transcriptomics. Through systematic comparative analyses, we delineate tumor transcriptional states and candidate cell-of-origin. More broadly, we demonstrate systematic molecular profiling of childhood cancers to orient oncogenic targeting for in vivo modeling, a critical resource for the study of rare tumors and development of therapeutics.

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Project description:Combining the results of a large scale proteomic analysis of human transcription factor interaction network with knowledge databases, we identified FOXR2 as one of the top-ranked candidate proto-oncogenes. Here, we show that FOXR2 forms a stable complex with MYC and MAX and subsequently regulates cell proliferation by promoting MYC’s transcriptional activities. We demonstrated that FOXR2 is highly expressed in several breast, lung, and liver cancer cell lines and related patient tumor samples, while reduction of FOXR2 expression in a xenograft model inhibits tumor growth. These results indicate that FOXR2 acts with MYC to promote cancer cell proliferation, which is a potential tumor-specific target for therapeutic intervention against MYC-driven cancers.

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