RAT-seq mapping of the FLI1 exonic circular RNA FECR1 target gene network in MDA-MB231 breast cancer cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE117727 | GEO | 2018/11/15
REPOSITORIES: GEO
Similar Datasets
Project description:RAT-seq mapping of the FLI1 exonic circular RNA FECR1 target gene network in MDA-MB231 breast cancer cells
| PRJNA483028 | ENA
Project description:MDA-MB-231 breast cancer cells were infected with either Ad-GFP, Ad-FLI1, or Ad-PDEF qPCR gene expression profiling of MDA-MB-231 breast cancer cells were infected with either Ad-GFP, Ad-FLI1, or Ad-PDEF.
2012-12-31 | E-GEOD-38499 | biostudies-arrayexpress
Project description:MDA-MB-231 breast cancer cells were infected with either Ad-GFP, Ad-FLI1, or Ad-PDEF
2012-12-31 | GSE38499 | GEO
Project description:BackgroundFriend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. However, little is known about the mechanisms underlying the activation of this proto-oncogene in tumors.ResultsImmunohistochemical staining showed that FLI1 is aberrantly overexpressed in advanced stage and metastatic breast cancers. Using a CRISPR Cas9-guided immunoprecipitation assay, we identify a circular RNA in the FLI1 promoter chromatin complex, consisting of FLI1 exons 4-2-3, referred to as FECR1.Overexpression of FECR1 enhances invasiveness of MDA-MB231 breast cancer cells. Notably, FECR1 utilizes a positive feedback mechanism to activate FLI1 by inducing DNA hypomethylation in CpG islands of the promoter. FECR1 binds to the FLI1 promoter in cis and recruits TET1, a demethylase that is actively involved in DNA demethylation. FECR1 also binds to and downregulates in trans DNMT1, a methyltransferase that is essential for the maintenance of DNA methylation.ConclusionsThese data suggest that FECR1 circular RNA acts as an upstream regulator to control breast cancer tumor growth by coordinating the regulation of DNA methylating and demethylating enzymes. Thus, FLI1 drives tumor metastasis not only through the canonical oncoprotein pathway, but also by using epigenetic mechanisms mediated by its exonic circular RNA.
| S-EPMC6290540 | biostudies-literature
Project description:Ewing sarcoma (EWS) is a malignant pediatric bone cancer. Most Ewing sarcomas are driven by EWS-FLI1 oncogenic transcription factor that plays roles in transcriptional regulation, DNA damage response, cell cycle checkpoint control, and alternative splicing. USP1, a deubiquitylase which regulates DNA damage and replication stress responses, is overexpressed at both the mRNA and protein levels in EWS cell lines compared to human mesenchymal stem cells, the EWS cell of origin. The functional significance of high USP1 expression in Ewing sarcoma is not known. Here, we identify USP1 as a transcriptional target of EWS-FLI1 and a key regulator of EWS cell survival. We show that EWS-FLI1 knockdown decreases USP1 mRNA and protein levels. ChIP and ChIP-seq analyses show EWS-FLI1 occupancy on the USP1 promoter. Importantly, USP1 knockdown or inhibition arrests EWS cell growth and induces cell death by apoptosis. We observe destabilization of Survivin (also known as BIRC5 or IAP4) and activation of caspases-3 and -7 following USP1 knockdown or inhibition in the absence of external DNA damage stimuli. Notably, EWS cells display hypersensitivity to combinatorial treatment of doxorubicin or etoposide, EWS standard of care drugs, and USP1 inhibitor compared to single agents alone. Together, our study demonstrates that USP1 is regulated by EWS-FLI1, the USP1-Survivin axis promotes EWS cell survival, and USP1 inhibition sensitizes EWS cells to standard of care chemotherapy.
2024-01-26 | PXD041033 | Pride
Project description:Proteomics characterization of KAIMRC1 cell line, a naturally immortalized breast cancer cells, is described in comparison to MCF7 and MDA-231 breast cancer cells. Quantitative proteomics analysis using the tandem mass tag (TMT) labeled technique in conjunction with phosphopeptide enrichment method was used to perform comparative profiling of proteins and phosphoproteins in the three cell lines. In total, 673 proteins and 33 Phosphoproteins were differentially expressed among these cell lines. These proteins are involved in several key cellular pathways that include DNA replication and repair, Splicing machinery, amino acid metabolism, cellular energy, and Estrogen signaling pathway. Many of the differentially expressed proteins are associated with different types of tumors including breast cancer. For validation, 4 highly significant expressed proteins including MTAP, KCTD12, PARP 1, and Prelamin-A/C were subjected to western blotting and the results were consistent with proteomics analysis. Unlike MCF-7 and MDA-MB-231, KAIMRC1 showed different phospho- and non-phosphoproteomic phenotypes which make it a potential model to study breast cancer.
2020-06-22 | PXD017721 | Pride
Project description:In the paper "Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers" by Bejjani et al., we identified Fra-1 and/or Fra-2 target genes in MDA-MB-231 cells. si RNA against Fra-1 and against Fra-2 were transfected in MDA-MB-231 cells either independenlty or simultaneously to identify genes regulated specifically by Fra-1 or Fra-2 and genes regulated redundantly or complementarily by Fra-1 and Fra-2 total RNA were purified and biotinylated sense-strand cDNA were produced. cDNA targets were used to probe Affymetrix GeneChip Human Gene 2.0 ST arrays
2021-02-23 | GSE146823 | GEO
Project description:Proteomics characterization of KAIMRC1 cell line, a naturally immortalized breast cancer cells, is described in comparison to MCF-7 and MDA-MB-231 breast cancer cells. Quantitative proteomics analysis using the tandem mass tag (TMT)-labeled technique in conjunction with the phosphopeptide enrichment method was used to perform comparative profiling of proteins and phosphoproteins in the three cell lines. In total, 673 proteins and 33 Phosphoproteins were differentially expressed among these cell lines. These proteins are involved in several key cellular pathways that include DNA replication and repair, splicing machinery, amino acid metabolism, cellular energy, and estrogen signaling pathway. Many of the differentially expressed proteins are associated with different types of tumors including breast cancer. For validation, 4 highly significant expressed proteins including S-methyl-5'-thioadenosine phosphorylase (MTAP), BTB/POZ domain-containing protein (KCTD12), Poly (ADP-ribose) polymerase 1 (PARP 1), and Prelamin-A/C were subjected to western blotting, and the results were consistent with proteomics analysis. Unlike MCF-7 and MDA-MB-231, KAIMRC1 showed different phospho- and non-phosphoproteomic phenotypes which make it a potential model to study breast cancer.
| S-EPMC7352455 | biostudies-literature
Project description:Although membrane-anchored PD-L1 has been well-studied for its engagement with PD-1 on T cells to evade anti-tumor immunity, whether PD-L1 regulate oncogenic signaling pathways in tumor cells remains elusive. Methods: Total RNA from MDA-MB-231 wild type (WT) , MDA-MB-231 PD-L1 knock-out (KO), CT26 WT or CT26 Pd-l1 KO cells was purified using Qiagen RNeasy mini kit (Qiagen) according to the manufacturer’s instructions. Library preparation and sequenceing analysis were performed at the Molecular Genetics Core facility in Dana-Farber Cancer institute. RNA-seq data was aligned using STAR v2.5.4a. Conclusions: Our study indicates that PD-L1 may regulate genes that are involved in immune response regulating pathways.
2020-06-07 | GSE134510 | GEO
Project description:Owing to its unique redox properties, cerium oxide (nanoceria) nanoparticles have been shown to confer either radiosensitization or radioprotection to human cells. We investigated nanoceria's ability to modify cellular health and reactive oxygen species (ROS) at various absorbed doses (Gray) of ionizing radiation in MDA-MB231 breast carcinoma cells. We used transmission electron microscopy to visualize the uptake and compartmental localization of nanoceria within cells at various treatment concentrations. The effects on apoptosis and other cellular health parameters were assessed using confocal fluorescence imaging and flow cytometry without and with various absorbed doses of ionizing radiation, along with intracellular ROS levels. Our results showed that nanoceria were taken up into cells mainly by macropinocytosis and segregated into concentration-dependent large aggregates in macropinosomes. Confocal imaging and flow cytometry data showed an overall decrease in apoptotic cell populations in proportion to increasing nanoparticle concentrations. This increase in cellular health was observed with a corresponding reduction in ROS at all tested absorbed doses. Moreover, this effect appeared pronounced at lower doses compared to unirradiated or untreated populations. In conclusion, internalized nanoceria confers radioprotection with a corresponding decrease in ROS in MDA-MB231 cells, and this property confers significant perils and opportunities when utilized in the context of radiotherapy.
| S-EPMC8614948 | biostudies-literature