Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The spliceosome is an exploitable vulnerability in RB1-mutant cancer

ABSTRACT: The spliceosome is an exploitable vulnerability in RB1-mutant cancer

PROVIDER: PRJNA606793 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11091600_1.fastq.gz	Fastqsanger.gz
	SRR11091600_2.fastq.gz	Fastqsanger.gz
	SRR11091601_1.fastq.gz	Fastqsanger.gz
	SRR11091601_2.fastq.gz	Fastqsanger.gz
	SRR11091602_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 114

Similar Datasets

The spliceosome is an exploitable vulnerability in RB1-mutant cancer

Project description:RB transcriptional corepressor 1 (RB1) is frequently mutated in human cancers, we discover a new target of oncogenic stress in RB1-mutant cells.

2022-03-31 | GSE145235 | GEO

HALTING THE NAD+-DEPENDENT DEACETYLASE SIRT6 UNVEILS SPLICEOSOME DEREGULATION AS EXPLOITABLE VULNERABILITY FOR AGGRESSIVE MYELOMA

Project description:HALTING THE NAD+-DEPENDENT DEACETYLASE SIRT6 UNVEILS SPLICEOSOME DEREGULATION AS EXPLOITABLE VULNERABILITY FOR AGGRESSIVE MYELOMA

| PRJNA869925 | ENA

HALTING THE NAD+-DEPENDENT DEACETYLASE SIRT6 UNVEILS SPLICEOSOME DEREGULATION AS EXPLOITABLE VULNERABILITY FOR AGGRESSIVE MYELOMA

Project description:Epigenetic defects play a major role in tumors, by promoting aggressiveness, drug resistance and disease progression. Targeting enzymes responsible for these changes holds promise but the knowledge-gap and lack of selective inhibitors severely hampers their clinical use. Recently, we found that Multiple Myeloma (MM) cells exhibit high level of NAD+-dependent deacetylase SIRT6 as an adaptive response to their intrinsic genomic instability. Here we focus on splicing-related events resulting as the most enriched pathways among MM patients with high SIRT6 levels. CoMMpass dataset analysis confirmed the prognostic role of SIRT6 in MM, with its presence correlating with poor outcome and aggressiveness. Transcriptome analysis of SIRT6-depleted MM cells indicated spliceosome perturbation as critical: chemical and genetic approaches resulted in enhanced anti-MM activity of spliceosome modulator Sudamycin D6 (SD6) thus supporting RNA splicing deregulation as vulnerability for these cells. Spliceosome is a therapeutic weakness for MYC-driven cancer, as such we found that while c-MYC oncogene loss shows resistance, its re-expression enhances efficacy of tested strategy. A direct role for SIRT6 on splicing factors genes was also demonstrated using ChIP-seq analyses. Overall, the dysregulated spliceosome activity triggered by epigenetic machinery blocking represents a novel therapeutic strategy for poor-prognosis subset of MM patients overexpressing c-MYC

2022-08-19 | GSE211342 | GEO

Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Broad Spectrum of Cancer Therapeutics and Confers Vulnerability to Replication Stress

Project description:Prostate cancers (PC) with loss of the potent tumor suppressors TP53 and RB1 exhibit poor outcomes that include resistance to androgen receptor (AR) pathway antagonists. TP53 and RB1 also influence cell plasticity and are frequently lost in PCs with neuroendocrine (NE) differentiation. Therapeutic strategies that address these aggressive variant PCs are urgently needed. Using deep genomic profiling of 410 metastatic biopsies, we determined the relationships between combined TP53 and RB1 loss and PC phenotypes. Notably, 40% of TP53/RB1 deficient tumors were classified as AR-active adenocarcinomas indicating that NE differentiation is not an obligate consequence of TP53/RB1 inactivation. A gene expression signature reflecting TP53/RB1 loss was associated with diminished responses to AR antagonists and reduced survival. These tumors exhibit high proliferation rates and evidence of elevated DNA repair processes. While tumor cells lacking TP53/RB1 were highly resistant to all single agent therapeutics, the combination of pharmacological PARP and ATR inhibition produced significant responses, reflecting a clinically-exploitable vulnerability resulting from replication stress.

2020-06-01 | GSE147250 | GEO

Murine Prostate Tissue: Rb1 null vs. Rb1 E2F binding deficient mutant

Project description:Transcriptional profilling of 60 day old prostate tissue from Rb1F/F:Trp53F/F:PB-Cre4 or Rb1R654W/F:Trp53F/F:PB-cre4 mice versus wild type prostate tissue. Profiles used to compare deregulation of known E2F target genes in prostate tissue expressing a mutant Rb1 gene to tissue lacking Rb1 expression. Tissue from two Rb1F/F:Trp53F/F:PB-Cre4 (null) mice or two Rb1654/F:Trp53F/F:PB-cre4 (mutant) mice compared to a pool of tissue from 3 wild type mice using two color arrays.

2010-11-27 | E-GEOD-25615 | biostudies-arrayexpress

Murine Prostate Tissue: Rb1 null vs. Rb1 E2F binding deficient mutant

2010-11-27 | GSE25615 | GEO

Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma

Project description:Resistance to proteasome inhibitors (PIs) is a ubiquitous clinical concern in multiple myeloma. We proposed that signaling-level responses after PI would reveal new means to enhance efficacy. Unbiased phosphoproteomics after the PI carfilzomib surprisingly demonstrated the most prominent phosphorylation changes on spliceosome components. Spliceosome modulation was invisible to RNA or protein abundance alone. Transcriptome analysis demonstrated broad-scale intron retention suggestive of PI-specific splicing interference. Direct spliceosome inhibition synergized with carfilzomib and showed potent anti-myeloma activity. Functional genomics and exome sequencing further supported the spliceosome as a specific vulnerability in myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma.

2020-02-21 | PXD012172 | Pride

Targeting the deacetylase SIRT6 unveils spliceosome deregulation as exploitable vulnerability for aggressive myeloma.

Project description: Not available

| S-EPMC10362259 | biostudies-literature

Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells

Project description:Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells

| PRJNA941940 | ENA

H3B-8800, a novel oral splicing modulator, induces lethality in spliceosome mutant cancers [K562]

Project description:Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factors SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Although cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, clinical means to therapeutically target the spliceosome do not currently exist. Here, we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and selectively kills spliceosome-mutant epithelial and hematologic malignancies. The effects of H3B-8800 are entirely selective for the Sf3b complex, as evidenced by the identification of drug-resistant cells bearing mutations in Sf3b components. Although H3B-8800 modulates RNA splicing mediated by WT or cancer-associated SF3B1 mutants, its preferential effects on spliceosome-mutant cells is due to preferred retention of short, GC-rich introns, which are enriched in genes encoding a substantial number of spliceosome components. These data demonstrate the therapeutic potential of splicing modulation in spliceosome-mutant cancers.

2017-12-20 | GSE94528 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data