Delineation of EZH2 oncogenic functions in hepatocellular carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE17733 | GEO | 2011/05/31
SECONDARY ACCESSION(S): PRJNA118385
REPOSITORIES: GEO
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Project description:The goal of this study was to delineate the important EZH2 direct target genes that mediate the oncogenic properties of EZH2 in HCC. The EZH2 direct target genes in two HCC cell lines were identified by chromatin immunoprecipitation microarray (ChIP-chip) analysis and later confirmed by independent ChIP-PCR. The functions of the target genes were further examined. Two human HCC cell lines, Huh7 and PLC/PRF/5 (PLC5), were grown in DMEM supplemented with 10% fetal bovine serum. ChIP assays were performed using anti-EZH2 antibody. The immunoprecipitated and input DNA were used to probe the Agilent human ChIP-chip arrays.
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2011-08-08 | GSE25884 | GEO
Project description:The goal of this study was to delineate the important AR direct target genes that mediate the oncogenic properties of AR in HCC. The AR direct target genes in two HCC cell lines were identified by chromatin immunoprecipitation microarray (ChIP-chip) analysis and later confirmed by independent ChIP-PCR. The functions of the target genes were further examined. Two human HCC cell lines, Huh7 and PLC/PRF/5 (PLC5), were grown in DMEM supplemented with 10% fetal bovine serum. ChIP assays were performed using anti-AR antibody. The immunoprecipitated and input DNA were used to probe the Agilent human ChIP-chip arrays.
2011-08-07 | E-GEOD-25884 | biostudies-arrayexpress
Project description:Polycomb group (PcG) proteins including EZH2, SUZ12 and so on, which specifically catalyze trimethylation of histone 3 lysine 27 (H3K27me3), and methylated H3K27 can be recognized by other specific binding proteins to compress chromatin structure, leading to the transcriptional repression of the target genes. To completely understand the epigenetic profile and molecular network of PcG in HCC, we performed ChIP-on-chip screens with EZH2, SUZ12 and H3K27me3 antibodies in HepG2 cells. Comparison of ChIP-on-chip results from EZH2, SUZ12 and H3K27me3.
2013-11-13 | E-GEOD-52300 | biostudies-arrayexpress
Project description:Chemotherapy resistance is the main impediment in the treatment of acute myeloid leukaemia (AML). Despite rapid advances, the various mechanisms that lead to resistance development remain to be defined in detail. Here we report that loss-of-function mutations (LOF) in the histone methyltransferase EZH2 have the potential to confer resistance against the chemotherapeutic agent cytarabine. We identify seven distinct EZH2 mutations leading to loss of H3K27 trimethylation via multiple mechanisms. Analysis of matched diagnosis and relapse samples reveal a heterogenous regulation of EZH2 and a loss of EZH2 in 50% of patients. We confirm that loss of EZH2 induces resistance against cytarabine in the cell lines HEK293T and K562 as well as in a patient-derived xenograft (PDX) model. Proteomics and transcriptomics analysis reveal that resistance is conferred by upregulation of multiple direct and indirect EZH2 target genes that are involved in apoptosis evasion, augmentation of proliferation and alteration of transmembrane transporter function. Our data indicates, that loss of EZH2 results in upregulation of its target genes, providing the cell with a selective growth advantage, which mediates chemotherapy resistance.
2021-03-12 | PXD023139 | Pride
Project description:Polycomb group (PcG) proteins including EZH2, SUZ12 and so on, which specifically catalyze trimethylation of histone 3 lysine 27 (H3K27me3), and methylated H3K27 can be recognized by other specific binding proteins to compress chromatin structure, leading to the transcriptional repression of the target genes. To completely understand the epigenetic profile and molecular network of PcG in HCC, we performed ChIP-on-chip screens with EZH2, SUZ12 and H3K27me3 antibodies in HepG2 cells.
2013-11-13 | GSE52300 | GEO
Project description:Purpose: Identify new targets in MYCN-amplified Neuroblastoma Methods: ChIP-Seq experiments were performed on Kelly and LAN-1 neuroblastoma cells by using the following antibodies: anti-EZH2 (Cell Signaling 5246S); anti-H3K27me3 (Millipore 07-449); anti-H3K4me3 (Abcam ab8580). We evaluated the global EZH2 PRC2-dependence by identifiying direct genome-wide target genes for EZH2, H3K27me3 and H3K4me3. Results: We found that EZH2 serves a PRC2-dependent function in neuroblastoma, repressing neuronal differentiation. Moreover, EZH2-regulated genes were strongly repressed in MYCN-amplified and high-risk primary tumors. Conclusion: Our study supports testing EZH2 inhibitors in patients with MYCN-amplified neuroblastoma.
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Project description:Epigenetic dysregulation is closely associated with the pathogenesis of hepatocellular carcinoma (HCC). Enhancer of zeste homolog 2 (EZH2) is a key protein involved in the exacerbation of various cancers, including HCC. Despite several clinical trials of epigenetic therapies targeting EZH2, the mechanisms underlying EZH2-mediated gene suppression in HCC are not fully understood. In this study, we investigated EZH2-mediated transcriptional programs under EZH2-selective inhibition through an integrative analysis of epigenomic (ATAC-seq) and transcriptomic (RNA-seq) approaches. To determine the impact of EZH2 dysfunction, we measured the levels of H3K27me3 and EZH2 expression using flow cytometry and reverse transcription quantitative real-time PCR (RT-qPCR), respectively. Notably, we found that higher expression of EZH2 was significantly correlated with poorer survival among HCC patients by reanalyzing transcriptomes in the cancer genome atlas (TCGA). Inhibition of EZH2 with Tazemetostat (EPZ-6438), a selective inhibitor of EZH2, showed that EZH2 regulates genes involved in lipid homeostasis, and cysteine-methionine metabolism. Among the 13 EZH2 target genes identified by transcriptomic and epigenomic profiling, we selected BHMT and CDO1, which were significantly associated with poor survival in HCC patients. When HCC cells were treated with Tazemetostat, the expression levels of the BHMT and CDO1 genes increased, while the expression levels of ferroptosis marker genes, such as FSP1, NFS1, and SLC7A11, decreased. This suggests that inhibiting EZH2 may have potential therapeutic benefits in HCC by regulating the expression of genes involved in important biological processes. Our study suggests that EZH2 epigenetically regulates ferroptosis by controlling cysteine metabolism in HCC.
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Project description:Epigenetic dysregulation is closely associated with the pathogenesis of hepatocellular carcinoma (HCC). Enhancer of zeste homolog 2 (EZH2) is a key protein involved in the exacerbation of various cancers, including HCC. Despite several clinical trials of epigenetic therapies targeting EZH2, the mechanisms underlying EZH2-mediated gene suppression in HCC are not fully understood. In this study, we investigated EZH2-mediated transcriptional programs under EZH2-selective inhibition through an integrative analysis of epigenomic (ATAC-seq) and transcriptomic (RNA-seq) approaches. To determine the impact of EZH2 dysfunction, we measured the levels of H3K27me3 and EZH2 expression using flow cytometry and reverse transcription quantitative real-time PCR (RT-qPCR), respectively. Notably, we found that higher expression of EZH2 was significantly correlated with poorer survival among HCC patients by reanalyzing transcriptomes in the cancer genome atlas (TCGA). Inhibition of EZH2 with Tazemetostat (EPZ-6438), a selective inhibitor of EZH2, showed that EZH2 regulates genes involved in lipid homeostasis, and cysteine-methionine metabolism. Among the 13 EZH2 target genes identified by transcriptomic and epigenomic profiling, we selected BHMT and CDO1, which were significantly associated with poor survival in HCC patients. When HCC cells were treated with Tazemetostat, the expression levels of the BHMT and CDO1 genes increased, while the expression levels of ferroptosis marker genes, such as FSP1, NFS1, and SLC7A11, decreased. This suggests that inhibiting EZH2 may have potential therapeutic benefits in HCC by regulating the expression of genes involved in important biological processes. Our study suggests that EZH2 epigenetically regulates ferroptosis by controlling cysteine metabolism in HCC.
2024-10-25 | GSE237951 | GEO
Project description:Epigenetic dysregulation is closely associated with the pathogenesis of hepatocellular carcinoma (HCC). Enhancer of zeste homolog 2 (EZH2) is a key protein involved in the exacerbation of various cancers, including HCC. Despite several clinical trials of epigenetic therapies targeting EZH2, the mechanisms underlying EZH2-mediated gene suppression in HCC are not fully understood. In this study, we investigated EZH2-mediated transcriptional programs under EZH2-selective inhibition through an integrative analysis of epigenomic (ATAC-seq) and transcriptomic (RNA-seq) approaches. To determine the impact of EZH2 dysfunction, we measured the levels of H3K27me3 and EZH2 expression using flow cytometry and reverse transcription quantitative real-time PCR (RT-qPCR), respectively. Notably, we found that higher expression of EZH2 was significantly correlated with poorer survival among HCC patients by reanalyzing transcriptomes in the cancer genome atlas (TCGA). Inhibition of EZH2 with Tazemetostat (EPZ-6438), a selective inhibitor of EZH2, showed that EZH2 regulates genes involved in lipid homeostasis, and cysteine-methionine metabolism. Among the 13 EZH2 target genes identified by transcriptomic and epigenomic profiling, we selected BHMT and CDO1, which were significantly associated with poor survival in HCC patients. When HCC cells were treated with Tazemetostat, the expression levels of the BHMT and CDO1 genes increased, while the expression levels of ferroptosis marker genes, such as FSP1, NFS1, and SLC7A11, decreased. This suggests that inhibiting EZH2 may have potential therapeutic benefits in HCC by regulating the expression of genes involved in important biological processes. Our study suggests that EZH2 epigenetically regulates ferroptosis by controlling cysteine metabolism in HCC.
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