Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pattern occupation of HDACs on chromatin determines PI3K/AKT inhibitor resistance in cancers [RNA-seq]

ABSTRACT: Pattern occupation of HDACs on chromatin determines PI3K/AKT inhibitor resistance in cancers [RNA-seq]

PROVIDER: PRJNA564800 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR10095436_1.fastq.gz	Fastqsanger.gz
	SRR10095436_2.fastq.gz	Fastqsanger.gz
	SRR10095437_1.fastq.gz	Fastqsanger.gz
	SRR10095437_2.fastq.gz	Fastqsanger.gz
	SRR10095438_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Pattern occupation of HDACs on chromatin determines PI3K/AKT inhibitor resistance in cancers [ChIP-seq]

Project description:Pattern occupation of HDACs on chromatin determines PI3K/AKT inhibitor resistance in cancers [ChIP-seq]

| PRJNA564807 | ENA

Pattern occupation of HDACs on chromatin determines PI3K/AKT inhibitor resistance in cancers [ChIP-seq]

Project description:Blocking BRD4 or HDACs induces paradoxically similar gene expression, comparably attenuates PI3K/AKT inhibitor resistance in multiple cancer cells.

2020-09-09 | GSE137207 | GEO

Pattern occupation of HDACs on chromatin determines PI3K/AKT inhibitor resistance in cancers [RNA-seq]

Project description:Blocking BRD4 or HDACs induces paradoxically similar gene expression, comparably attenuates PI3K/AKT inhibitor resistance in multiple cancer cells.

2020-09-09 | GSE137200 | GEO

An epigenetic vulnerability in PI3K/AKT inhibition resistant cancers is targetable by both bromodomain and HDAC inhibitors

Project description:Acquisition of resistance to PI3K/AKT-targeted monotherapy regardless of cancer types implies the existence of common mechanisms. Here we demonstrate that while causing glycolysis crisis, acetyl-CoA shortage and global decrease of histone acetylation, PI3K/AKT inhibitors induce drug resistance by selectively augmenting CBP/p300, H3K27 acetylation and BRD4 binding at genomic loci of a subset of growth factor and receptor (GF/R) genes. BRD4 occupation at these loci and drug resistant cell growth are vulnerable to both bromodomain and HDAC inhibitors. Little or none occupation of HDACs at the GF/R gene loci underscores the paradox that cells respond equivalently to the two classes of inhibitors with opposite modes of action. Targeting this unique epigenetic vulnerability offers a general solution to overcome PI3K/AKT inhibitor resistance in different cancers.

2020-09-09 | GSE147455 | GEO

PI3K-AKT activation determines oncogenic RAS-induced hypertranscription and replication stress

Project description:PI3K-AKT activation determines oncogenic RAS-induced hypertranscription and replication stress

| PRJNA1430343 | ENA

Transcription profiling of transgenic mice constitutively active for caPI3K and dominant-negative forms of PI3K (dnPI3K) to test if the insulin/IGF-IRS-PI3K-Akt determines organ size in vertebrates

Project description:The insulin/IGF-IRS-PI3K-Akt pathway is highly conserved in evolution. To test whether this signaling cascade determines organ size in vertebrates, we have recently created mouse lines transgenic for constitutively active (caPI3K) and dominant-negative forms of PI3K (dnPI3K) (Shioi et al., 2000). Transgene expression is driven by the cardiac-specific a -myosin heavy chain (MHC) promoter. Both transgenic lines are characterized by moderate but highly consistent changes in heart size, despite the fact that body weight and the size of other organs are completely normal. caPI3K transgenic animals have hearts 20% larger than those of wild type littermates, whereas dnPI3K mice have hearts that are 17% smaller. The observed changes in heart size correlate with an appropriate increase or decrease in the size of transgenic cardiomyocytes. These hearts do not have cardiomyopathic changes, since the contractile function of transgenic hearts is normal, and signs of necrosis, apoptosis, or interstitial fibrosis are absent (see Physiology). These data suggest an autonomous role for PI3K in cell size regulation. Our goal is now to determine how activation of this system translates into changes in cell size by identifying the trigger and components of this signaling cascade. Heterozygous caPI3K (constitutively active PI3K) and dnPI3K (dominant-negative PI3K) transgenic female mice (5-14 months) compared with non-transgenic littermates. Transgene expression driven by the a -myosin heavy chain (a -MHC) promoter.

2007-12-13 | E-GEOD-558 | biostudies-arrayexpress

PI3K-AKT activation determines oncogenic RAS-induced hypertranscription and replication stress [ChrRNAseq]

Project description:PI3K-AKT activation determines oncogenic RAS-induced hypertranscription and replication stress [ChrRNAseq]

| PRJNA1430363 | ENA

PI3K-AKT activation determines oncogenic RAS-induced hypertranscription and replication stress [RNASeq]

Project description:PI3K-AKT activation determines oncogenic RAS-induced hypertranscription and replication stress [RNASeq]

| PRJNA1430365 | ENA

PI3K-AKT activation determines oncogenic RAS-induced hypertranscription and replication stress [RNASeq]

Project description:Oncogenic RAS activation, hypertranscription and transcription-replication conflicts (TRCs) are frequent features of cancer cells that are under investigation for therapeutic targeting. RAS oncogenes promote RNA polymerase activity and hypertranscription for cell growth and proliferation, which can the lead to TRCs. Here, we investigated hypertranscription and replication stress induced by the HRAS and KRAS oncogenes, and their downstream signalling through the MAPK and PI3K pathways. We show that HRAS causes more TRCs than KRAS because HRAS specifically hyperactivates the PI3K-AKT signalling pathway. MAPK signalling is insufficient to cause hypertranscription and TRCs, which require PI3K activity. PI3K hyperactivation was associated with increased E2F and MYC transcription programmes, increased S phase entry, increased nascent transcription of genes encoding ribosome biogenesis factors and expression of small nucleolar RNAs (snoRNAs). Inhibiting S phase entry alone did not rescue hypertranscription and replication stress, which required both MAPK and PI3K signalling. We report that a main downstream effector of PI3K-induced hypertranscription is AKT-mediated phosphorylation of GSK3b, which stabilises MYC. Cancer datasets further support that PI3K mutations may be associated with hypertranscription and replication stress signatures. Our findings suggest a mechanistic explanation for replication stress variability across RAS models and identify potential new predictors of TRCs in cancer.

2026-03-09 | GSE322525 | GEO

PI3K-AKT activation determines oncogenic RAS-induced hypertranscription and replication stress [ChrRNAseq]

2026-03-09 | GSE322524 | GEO