Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HDAC Inhibitor-Induced Acetylation of KRAS Confers A Pro-Oncogenic Effect Limiting Treatment Response in Colorectal Cancer

ABSTRACT: HDAC Inhibitor-Induced Acetylation of KRAS Confers A Pro-Oncogenic Effect Limiting Treatment Response in Colorectal Cancer

PROVIDER: PRJNA422779 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6384810_1.fastq.gz	Fastqsanger.gz
	SRR6384810_2.fastq.gz	Fastqsanger.gz
	SRR6384820_1.fastq.gz	Fastqsanger.gz
	SRR6384820_2.fastq.gz	Fastqsanger.gz
	SRR6384830_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 80

Similar Datasets

HDAC Inhibitor-Induced Acetylation of KRAS Confers A Pro-Oncogenic Effect Limiting Treatment Response in Colorectal Cancer

Project description:The limited clinical utility of HDAC inhibitors for the treatment of colorectal cancer (CRC) has until now remained an unresolved conundrum. Our findings provide comprehensive mechanistic insight into the ineffectiveness that defines HDAC inhibitors as a monotherapy for CRC. We identified that inhibition of HDAC2 promotes the emergence of a super-oncogenic KRAS by inducing K5 acetylation that fosters a previously undiscovered electrostatic interaction with R67 conserved in RAF kinases. This post-translational modification facilitates an increase in the binding affinity to this family of downstream RAS effectors, which translates into an immediate and persistent hyperactivation of the downstream MAPK-signaling. The concomitant instability of its co-conspirator c-MYC enables cells selectively harboring oncogenic KRAS to enter a protective state of reversible cell cycle arrest characterized by a senescence-like phenotype. Demonstratively, preventing this phenomenon from taking place provides a compelling alternative strategy for improving the prospects of HDAC inhibitor treatment for CRC.

2019-03-31 | GSE108191 | GEO

Pharmacological HDAC inhibition attenuates cardiac hypertrophy and histone acetylation of target genes

Project description:Cardiac hypertrophy is characterized by an increase in heart size and profound gene expression changes. Pharmacological histone deacetylase (HDAC) inhibitors attenuate pathological cardiac remodeling and hypertrophic gene expression. Published literature has linked enzymes that mediates histone acetylation to pathogenesis, however, the role of histone acetylation to define hypertrophic gene regulatory events are not well understood. We used chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (seq) to comprehensively examine genome-wide histone acetylation changes in a pre-clinical model of pathological cardiac hypertrophy by transverse aortic constricted (TAC). We examined the gene targets conferred by the prototypical HDAC inhibitor Trichostatin A (TSA). TSA induces genome-wide histone acetylation and deacetylation in the heart. Alterations to histone acetylation were found on genes involved in cardiac morphology such as cardiac contraction, collagen deposition, inflammation and extracellular matrix. Gene set enrichment analysis identified NF-kappa B (NFKB), as a transcription factor positively correlated with TAC and negatively correlated with TSA by ChIP-seq. Histone acetylation on the promoters of NKFB target genes was increased, consistent with gene activation. In contrast, the promoters of these genes were deacetylated by TSA in hypertrophic animals and reduced expression of NFKB target genes. Our results suggest a potential mechanism for TSA mediated cardioprotection conferred by histone deacetylation of target genes implicating the importance of inflammation. ChIP-seq profiles for histone acetylation in left ventricles of mice that develop cardiac hypertrophy and treated with HDAC inhibitors were generated by deep sequencing, using Illumina GAIIx.

2015-04-25 | E-GEOD-63590 | biostudies-arrayexpress

BCL6 confers KRAS-mutant NSCLCs resistance to BET inhibitors

Project description:BCL6 confers KRAS-mutant NSCLCs resistance to BET inhibitors

| PRJNA486332 | ENA

Pharmacological HDAC inhibition attenuates cardiac hypertrophy and histone acetylation of target genes

2015-04-25 | GSE63590 | GEO

Molecular changes in cancer cells exposed to an HDAC inhibitor: A metabolomics approach

Project description:Histone deacetylase (HDAC) inhibitors are part of a new generation of epigenetic drugs for cancer treatment. It is known that histone acetylation plays a key role in controlling essential chromosome functions, including gene regulation, and this process has been linked with cancer development and progression. Better understanding of molecular mechanisms involving HDAC inhibitors is needed for the design of new targeted drugs, and also to evaluate the effectiveness of current treatments. In this study, an untargeted metabolomics approach was used to identify intracellular metabolite deregulation after treating cancer cell lines with the HDAC inhibitor HC-Toxin. Metabolomics analysis was performed using high resolution mass spectrometry, in combination with univariate and multivariate statistics and pathway analysis. HDAC inhibition showed highly specific metabolic changes in cancer cell lines compared to non-cancerous cells. In particular, N-acetyl-L-cysteine, N-acetylmethionine, and N-acetyl-L-carnitine showed a dose dependent change. Moreover, pathways controlling protein biosynthesis, as well as tryptophan, cysteine and methionine metabolism were significantly altered by HDAC inhibition. This study illustrates that HDAC inhibition has multiple effects on different metabolic pathways and our results can be extrapolated to inform on the molecular transitions in human cells.

2022-05-04 | MTBLS682 | MetaboLights

HDAC inhibitors result in widespread alteration of the histone acetylation landscape and BRD4 targeting to gene bodies

Project description:Histone acetylation is associated with active transcription and serves as a binding site for reader proteins that function in transcriptional initiation and elongation. Histone acetylation levels are regulated through the actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs) that antagonistically control the overall balance of this posttranslational modification. HDAC inhibitors (HDACi) are potent agents that disrupt this balance and are used clinically to treat a range of human diseases including cancer. Despite their clinical applications, little is known about their chromatin effects. By applying quantitative genomic and proteomic approaches, we demonstrate that HDACi robustly increase a low abundance histone acetylation state (H4 K5ac/K8ac/12ac/K16ac), which serves as a preferred binding substrate for a variety of human bromodomain-containing proteins, including BRD4. This H4 polyacetylation signature observed after HDACi treatment accumulates in the transcribed regions of genes and correlates with the targeting of BRD4 to genes with increased gene expression. Collectively, these results suggest that HDAC inhibition functions, at least in part, through expansion of a rare chromatin acetylation state, which then retargets lysine-acetyl reader proteins associated with changes in gene expression.

2020-10-20 | GSE159620 | GEO

BCL6 confers KRAS-mutant NSCLCs resistance to BET inhibitors [ChIP-Seq]

Project description:BCL6 confers KRAS-mutant NSCLCs resistance to BET inhibitors [ChIP-Seq]

| PRJNA490505 | ENA

HDAC complex non-enzymatic inhibitor confers therapeutic effects with minimal transcriptomic changes

Project description:HDAC complex non-enzymatic inhibitor confers therapeutic effects with minimal transcriptomic changes

| PRJNA870965 | ENA

Effect of HDAC inhibitors on acetylated histones in P. pacificus

Project description:Western Blot showed that epigenetic control of the mouth dimorphism in P. pacificus correlates with histone 4 acetylation. This result was validated by mass spectrometry. This experiment profiled histone acetylation in the presence and absence of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA). Histone acetylation was also examined in the presence of another HDAC inhibitor (Na-butyrate), which served as an additional negative control because unlike TSA, it did not induce a phenotypic change.

2023-02-24 | PXD018940 | Pride

KRAS and MEK activation promote antisense oligonucleotide uptake and activity by limiting collagen production

Project description:KRAS and MEK activation promote antisense oligonucleotide uptake and activity by limiting collagen production

| PRJNA723544 | ENA