Expression data from ovarian cancer cell line OVCAR3 following Knockdown or Knockout of BORIS (CTCFL)
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PROVIDER: PRJNA534124 | ENA |
REPOSITORIES: ENA
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Project description:The identification of prognostic biomarkers is a priority for patients suffering from high-grade serous ovarian cancer (SOC), which accounts for >70% of ovarian cancer (OC) deaths. Meanwhile borderline ovarian cancer (BOC) is a low malignancy tumor and usually patients undergo surgery with low probabilities of recurrence. However, SOC remains the most lethal neoplasm due to the lack of biomarkers for early diagnosis and prognosis. In this regard BORIS (CTCFL), a CTCF paralog, is a promising cancer biomarker that is overexpressed and controls transcription in several cancer types, mainly in OC. Studies suggest that BORIS has an important function in OC by altering gene expression, but the effect and extent to which BORIS influences transcription in OC from a genome-wide perspective is unclear. Here we sought to identify BORIS target genes in an OC cell line (OVCAR3) with potential biomarker use in OC tumor samples. To achieve this, we performed in vitro knockout (KO) and knockdown (KD) experiments of BORIS in OVCAR3 cell line followed by expression microarrays and bioinformatics network enrichment analysis to identify relevant BORIS target genes.
2019-07-31 | GSE130163 | GEO
Project description:The study involved transcriptome analysis using RNA-seq knockdown of BORIS/CTCFL gene expression in K652 cancer cell line using inducible shRNA. The K562 cell line is the only cancer cell line that is known to be dependent on BORIS for proliferation and self-renewal of stemness. The goal of the study was to investigate the early/immediate transcriptional response to BORIS downregulation (over 10-fold reduction in protein level) using an inducible shRNA.
2017-09-25 | GSE99825 | GEO
Project description:The study involved transcriptome analysis using RNA-seq knockdown of BORIS/CTCFL gene expression in K652 cancer cell line using inducible shRNA. The K562 cell line is the only cancer cell line that is known to be dependent on BORIS for proliferation and self-renewal of stemness. The goal of the study was to investigate the early/immediate small RNA transcriptional response to BORIS downregulation (over 10-fold reduction in protein level) using an inducible shRNA.
2017-09-25 | GSE99899 | GEO
Project description:High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecological cancer death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in a large proportion of ovarian cancers, which is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its functional role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cell of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14, a glycosyltransferase gene previously implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 co-expression in several human cancers. Finally, ChIP-seq demonstrated that expression of BORIS in FTSEC cells was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy.
2019-07-01 | GSE131931 | GEO
Project description:A common aberration in cancer is the activation of germline-specific proteins. The DNA-binding proteins among them generate novel chromatin states, not found in normal cells. The chromatin architecture protein CTCF has a germline-specific paralog BORIS/CTCFL, which is often erroneously activated in cancers. Another common feature of malignancies is the changed expression and epigenetic states of genomic repeats. The investigation of BORIS and CTCF binding to DNA repeats in cancer cell lines by ChIP-chip revealed three classes: elements cohabited by BORIS and CTCF, CTCF-bound only, or BORIS-only.
2016-08-17 | GSE84326 | GEO
Project description:Melanoma is the deadliest form of skin cancer, due to its tendency to metastasize early. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcription regulator that becomes ectopically expressed in melanoma. We recently showed that BORIS contributes to melanoma phenotype switching by altering the gene expression program of proliferative melanoma cells in favor of a more invasive phenotype. However, how BORIS alters the transcriptome remains unclear. Here, ATAC-seq was used to study BORIS-mediated chromatin accessibility alterations in proliferative melanoma cells. Genes that gained promoter accessibility following ectopic BORIS expression, were enriched for melanoma-specific invasive genes as well as invasion-associated biological processes, while promoters of genes associated with proliferation show reduce accessibility. Integration of ATAC-Seq and RNA-Seq data demonstrates that increased chromatin accessibility is associated with transcriptional upregulation of genes involved in tumor progression processes, and the aberrant activation of oncogenic transcription factors, while reduced chromatin accessibility and downregulated genes, were associated with repressed activity of tumor suppressors. Together, these findings indicate that BORIS mediates transcriptional reprogramming in melanoma cells by altering chromatin accessibility and gene expression, shifting the cellular transcription landscape of proliferative melanoma cells towards a pro-invasive genetic signature.
2023-04-21 | GSE211800 | GEO
Project description:Pervasive usage of alternative promoters leads to deregulation of gene expression in carcinogenesis and may drive the emergence of new genes in spermatogenesis. However, little is known regarding the mechanisms underpinning the activation of alternative promoters. In our present study, we uncovered a novel mechanism by which alternative cancer-testis-specific transcription is activated from the intergenic and intronic clustered CTCF binding sites, which are transcriptionally inert in normal somatic cells. BORIS/CTCFL, a paralog of CTCF with cancer-testis-specific expression forms a heterodimer with CTCF at the clustered binding sites thus triggering epigenetic reprogramming of these sites into units of active transcription. BORIS binding to CTCF sites leads to the recruitment of chromatin-remodeling factor SRCAP, with subsequent replacement of H2A histone with H2A.Z, therefore creating a more relaxed chromatin state in the nucleosomes flanking the clustered binding sites. This facilitates opening of chromatin beyond CTCF/BORIS binding sites and paves the way to the recruitment of multiple additional transcription factors, thereby activating transcription from a given binding site. We demonstrate that the CTCF binding sites, epigenetically reprogrammed by ectopic BORIS expression can drive the expression of cancer-testis genes, long-noncoding RNAs, retro-pseudogenes, and dormant transposable elements harbored by activated long transcripts. Taking together, our results reveal that BORIS functions as a transcription factor that epigenetically reprograms clustered CTCF binding sites into transcriptional start sites, promoting transcription from alternative promoters in both germ cells and cancer cells.
2024-01-03 | GSE207058 | GEO
Project description:To identify differentially expressed genes in Boris KO testis, gene expression profilings were performed with NIAID mouse customized arrays. Gene expressions of five biological replicates of Boris KO testis were compared to those of wild type testis. Total RNAs from WT and BORIS KO testes prepared from P14 mice were labelled with Cy5 and Cy3, respectively. Five sets of each genotype were studied.
2010-06-05 | E-GEOD-19162 | biostudies-arrayexpress
Project description:High-grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy due to the lack of reliable biomarkers, effective treatment and chemoresistance. Improving the diagnosis and the development of targeted therapies is still needed. The molecular pathomechanisms driving HGSC progression are not fully understood though crucial for effective diagnosis and identification of novel targeted therapy options. The oncogene CTCFL (BORIS), the paralog of CTCF, is a transcriptional factor highly expressed in ovarian cancer (but in rarely any other tissue in females) with cancer-specific characteristics and therapeutic potential. In this work, we seek to understand the regulatory functions of CTCFL to unravel new target genes with clinical relevance. We used in vitro models to evaluate the transcriptional changes due to the presence of CTCFL, followed by a selection of gene candidates using de novo network enrichment analysis. The resulting mechanistic candidates were further assessed regarding their prognostic potential and druggability. We show that CTCFL-driven genes are involved in cytoplasmic membrane functions; in particular, the Pi3K-AKT initiators EGFR1 and VEGFA, as well as ITGB3 and ITGB6 are potential drug targets. Finally, we identified the CTCFL targets ACTBL2, MALT1 and PCDH7 as mechanistic biomarkers to predict survival in HGSC. Finally, we elucidated the value of CTCFL in combination with its targets as a prognostic marker profile for HGSC progression and as putative drug targets.
2021-12-15 | GSE166767 | GEO
Project description:RNA-seq and small RNA-seq analysis of BORIS/CTCFL knockdown in K562 cell line
| PRJNA389991 | ENA