Project description:We proved that histone H3K27me3 and H3K27ac were elevated in AT/RT cells and distributed in distinct chromatin regions to regulate specific gene expression and to promote AT/RT growth. Targeting EZH2 and BRD4 activity is therefore a potential combination therapy for AT/RT.

2022-02-10 | GSE196440 | GEO

Therapeutic Targeting of EZH2 and BET BRD4 in Pediatric Rhabdoid Tumor [RNA-Seq]

2022-02-06 | GSE196057 | GEO

Therapeutic Targeting of EZH2 and BET BRD4 in Pediatric Rhabdoid Tumor [ChIP-Seq]

2022-02-06 | GSE196056 | GEO

Therapeutic Targeting of EZH2 and BET BRD4 in Pediatric Rhabdoid Tumors.

Project description:Aberrant activity of the H3K27 modifiers EZH2 and BRD4 is an important oncogenic driver for atypical teratoid/rhabdoid tumor (AT/RT), and each is potentially a possible therapeutic target for treating AT/RT. We, therefore, determined whether targeting distinct histone modifier activities was an effective approach for treating AT/RT. The effects of EZH2 and BRD4 inhibition on histone modification, cell proliferation, and cell invasion were analyzed by immunoblotting, MTS assay, colony formation assay, and cell invasion assay. RNA- and chromatin immunoprecipitation-sequencing were used to determine transcriptional and epigenetic changes in AT/RT cells treated with EZH2 and BRD4 inhibitors. We treated mice bearing human AT/RT xenografts with EZH2 and BRD4 inhibitors. Intracranial tumor growth was monitored by bioluminescence imaging, and the therapeutic response was evaluated by animal survival. AT/RT cells showed elevated levels of H3K27 trimethylation (H3K27me3) and H3K27 acetylation (H3K27ac), with expression of EZH2 and BRD4, and lack of SMARCB1 proteins. Targeted inhibition of EZH2 and BRD4 activities reduced cell proliferation and invasiveness of AT/RT in association with decreasing H3K27me3 and H3K27ac. Differential genomic occupancy of H3K27me3 and H3K27ac regulated specific gene expression in response to EZH2 and BRD4 inhibitions. A combination of EZH2 and BRD4 inhibition increased the therapeutic benefit in vitro and in vivo, outperforming either monotherapy. Overall, histones H3K27me3 and H3K27ac were elevated in AT/RT cells and distributed in distinct chromatin regions to regulate specific gene expression and to promote AT/RT growth. Targeting EZH2 and BRD4 activity is, therefore, a potential combination therapy for AT/RT.

| S-EPMC9081147 | biostudies-literature

Effect of EZH2 and BET bromodomain inhibition, alone and combined, on NUT carcinoma gene expression

Project description:To determine mechanisms of synergy between EZH2 and BRD4-NUT, we treated NUT carcinoma cell lines with EZH2 inhibitor, tazemetostat, and/or BET bromodomain inhibitors (ABBV075 pan-BET inhibitor or ABBV744 BD2-selective inhibitor). We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different NUT carcinoma cell lines at two time points, 6h and 96h.

2023-10-05 | GSE208774 | GEO

Therapeutic Targeting of EZH2 and BET BRD4 in Pediatric Rhabdoid Tumor

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

2022-02-06 | GSE196058 | GEO

Genomic Sequencing of Pediatric Rhabdoid Cancers

Project description:Genomic Sequencing of Pediatric Rhabdoid Cancers

| PRJNA169040 | ENA