Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq for dual BET/p300 inhibitors in pancreactic cancer cells

ABSTRACT: The goals of this study are to compare transcriptome profiling (RNA-seq) of seletive BET inhibitior, combiantion of BET and p300 inhibitor, and dual BET/p300 inhibitor in pancreatic cancer model (PANC1 cells) and study the anticancer mechanism. Using an optimized data analysis workflow, we mapped about 20 million sequence reads per sample to the human genome (build hg38) using Burrows Wheeler Aligner- Maximum Exact Match (BWA MEM) algorithm. The raw count for each gene was quantified using the general purpose read summarization function, featureCounts gainst ENSEMBL genes. Differential analysis was performed using edgeR, including a batch effect correction for batch effects. Geneset enrichment analysis based on the differential analysis idenfied few essential pathways that was the mechansim of action, including KRAS, TGFb, etc.

ORGANISM(S): Homo sapiens

PROVIDER: GSE192903 | GEO | 2022/01/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Acute resistance to BET inhibitors remodels compensatory transcriptional programmes via p300 co-activation

Project description:Aiming to discover anticipatory combination treatments for better and longer disease response rates, we here explore immediate epigenetic and transcriptional reactions after BET inhibition. BET inhibitor-driven decommissioning of BRD4 from chromatin is followed by an acute compensatory feedback loop intended to attenuate the loss of transcription. Critically, this adaptation occurs almost exclusively at key AML maintenance genes and is co-mediated by p300. However, this also provides a rationale therapeutic opportunity, with BET- followed by p300 inhibition. Of note, the transcriptional programs that p300 regulates to induce resistance to BET inhibition differ between AML subtypes. In some AMLs, p300 regulates transitional transcriptional patterns that allow homeostatic adjustments during earlier stages of resistance to BET inhibition, so that the importance of p300 is highest during initial resistance stages. In other AMLs, p300 leads to a linear induction of resistance to BET inhibition and, therefore, remains crucial throughout all stages of acquisition of resistance.

2023-10-01 | GSE167163 | GEO

Combined targeting of the BRD4-NUT-p300 axis in NUT midline carcinoma by dual selective bromodomain inhibitor, NEO2734

Project description:NUT midline carcinoma (NMC) is a rare, aggressive subtype of squamous carcinoma that is driven by the BRD4-NUT fusion oncoprotein. BRD4, a BET protein, binds to chromatin through its two bromodomains, and NUT recruits the p300 histone acetyltransferse (HAT) to activate transcription of oncogenic target genes. BET selective bromodomain inhibitors have demonstrated on-target activity in NMC patients, but with limited efficacy. P300, like BRD4, contains a bromodomain. We show that combining selective p300/CBP and BET bromodomain inhibitors, GNE-781 and OTX015, respectively, induces synergistic inhibition of NMC growth. Treatment of NMC cells with the novel dual p300/CBP and BET bromodomain selective inhibitor, NEO2734, potently inhibits growth and induces differentiation of NMC cells in vitro; findings that correspond with potentiated transcriptional effects from combined BET and p300 bromodomain inhibition. In three disseminated NMC xenograft models, NEO2734 provided greater growth inhibition, with tumor regression and significant survival benefit seen in two of three models, compared with a lead clinical BET inhibitor or 'standard' chemotherapy.

2020-06-19 | GSE142481 | GEO

Effect of the BET inhibitor, JQ1, on gene expression in triple-negative breast cancer cell lines

Project description:To study the effect of BET inhibition on gene expression in triple-negative breast cancer cells, we treated MDA-MB-231 and HCC70 cells with vehicle or the prototypical BET inhibitor, JQ1, for 72 hours. By comparing the expression profiles of vehicle-treated versus JQ1-treated cells, we can identify genes that respond to BET inhibition. The Affymetrix Human Gene 2.0. St Microarray were processed with RMA (robust multichip average algorithm) as implemented in Bioconductor package oligo, where background subtraction, quantile normalization and summarization (via median-polish) was accomplished. The top differentially expressed genes were identified using empirical Bayesian procedure of limma package. FDR method was selected to adjust the p-values for multiple testing.

2019-03-16 | GSE79332 | GEO

Hematopoietic transcription factors and p300/CBP shape the effects of BET bromodomain inhibition in leukemia [RNA-Seq]

Project description:The bromodomain and extraterminal (BET) protein Brd4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that Brd4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) Pu.1, Fli1, Erg, C/EBPα, C/EBPβ, and Myb at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate Brd4 recruitment to their occupied sites to promote transcriptional activation. Moreover, chemical inhibition of BET bromodomains is found to suppress the functional output each hematopoietic TF, thereby interfering with essential lineage-specific transcriptional circuits in this disease. These findings reveal a chromatin-based signaling cascade comprised of hematopoietic TFs, p300/CBP, and Brd4, which supports leukemia maintenance and is suppressed by BET bromodomain inhibition. PolyA selected RNA-Seq for drug treated or shRNA-expressing MLL-AF9 transformed acute myeloid leukemia cells (RN2)

2015-05-01 | E-GEOD-66068 | biostudies-arrayexpress

Hematopoietic transcription factors and p300/CBP shape the effects of BET bromodomain inhibition in leukemia [ChIP-Seq]

Project description:The bromodomain and extraterminal (BET) protein Brd4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that Brd4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) Pu.1, Fli1, Erg, C/EBPα, C/EBPβ, and Myb at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate Brd4 recruitment to their occupied sites to promote transcriptional activation. Moreover, chemical inhibition of BET bromodomains is found to suppress the functional output each hematopoietic TF, thereby interfering with essential lineage-specific transcriptional circuits in this disease. These findings reveal a chromatin-based signaling cascade comprised of hematopoietic TFs, p300/CBP, and Brd4, which supports leukemia maintenance and is suppressed by BET bromodomain inhibition. ChIP-Seq for regulatory factors of Brd4 in MLL-AF9 transformed acute myeloid leukemia cells (RN2)

2015-05-01 | E-GEOD-66122 | biostudies-arrayexpress

A549 cell treated with DDP+TSA vs DDP

Project description:analysis how HDAC inhibitior TSA increase cispkatin cytotoxicity

2024-06-23 | PXD052203 | Pride

Genome-wide analysis of gene expression in NMC cell line HCC2429 incubated with A-485 and JQ1 alone or combined

Project description:P300/CBP and BET inhibition have synergistic effects in NMC. To explore the molecular mechanisms of this synergistic effect, transcriptomic profiling was performed in HCC2429 cells incubated with 250 nM A-485 and 50 nM JQ1 alone or combined.

2020-04-07 | E-MTAB-8955 | biostudies-arrayexpress

Project description:MEM+TET

| PRJNA564090 | ENA

BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia [ChIP-Seq]

2015-05-01 | GSE66122 | GEO

BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia [RNA-Seq]

2015-05-01 | GSE66068 | GEO