Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Splicing targeting approaches highlight actionable vulnerabilities in triple negative breast cancer

ABSTRACT: To investigate if pharmacological inhibition of splicing could uncover novel actionable vulnerabilities in TNBC, we profiled the genome-wide transcriptional changes elicited in MDA-MB-231 cells by treatment with Indisulam, that promote degradation of the splicing, and Pladienolide B, that impairs the activity of SF3B1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE254842 | GEO | 2025/03/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Splicing targeting approaches highlight actionable vulnerabilities in advanced prostate cancer [22Rv1]

Project description:To investigate if pharmacological inhibition of splicing could uncover novel actionable vulnerabilities in CRPC, we profiled the genome-wide transcriptional changes elicited in 22Rv1 cells by treatment with three drugs that inhibit the splicing through different molecular targets: i. Pladienolide B, that impairs the activity of SF3B1; ii. Indisulam that promote degradation of the splicing factor RBM39; iii. THZ531 inhibits the cyclin dependent kinases (CDK) 12 and 13.

2024-03-06 | GSE234734 | GEO

Splicing targeting approaches highlight actionable vulnerabilities in triple negative breast cancer

Project description:Splicing targeting approaches highlight actionable vulnerabilities in triple negative breast cancer

| PRJNA1072064 | ENA

Splicing targeting approaches highlight actionable vulnerabilities in advanced prostate cancer [22Rv1]

Project description:Splicing targeting approaches highlight actionable vulnerabilities in advanced prostate cancer [22Rv1]

| PRJNA982834 | ENA

SF3B1 inhibitor pladienolide B induces pyroptosis of ovarian cancer cells

Project description:In order to explore the effect of SF3B1 inhibitor, pladienolide B, on ovarian cancer cells, OVCAR8 cells were treated with DMSO or 2nM pladienolide B for 72h. Cells were collected and performed RNA sequencing.

2023-11-25 | GSE222199 | GEO

CBX5 loss drives EGFR inhibitor resistance and results in therapeutically actionable vulnerabilities in lung cancer

Project description:CBX5 loss drives EGFR inhibitor resistance and results in therapeutically actionable vulnerabilities in lung cancer

| PRJNA471762 | ENA

Splicing Modulators Act at the Branch Point Adenosine Binding Pocket Defined by the PHF5A-SF3b Complex

Project description:Developing small-molecule splicing modulators represents a promising therapeutic approach for various diseases. Natural products such as pladienolide, herboxidiene, and spliceostatin have been identified as potent splicing modulators that target SF3B1 in the SF3b subcomplex. Using integrated chemogenomic, structural and biochemical approaches, we show that PHF5A, another core component of the SF3b complex, is also targeted by these compounds. Mutations in PHF5A-Y36, SF3B1-K1071, SF3B1-R1074, and SF3B1-V1078 confer resistance to these modulators, suggesting a common site of interaction. Whole-transcriptome RNA-seq analysis reveals that PHF5A-Y36C has minimal effect on basal splicing but alters the action of splicing modulators from inducing intron-retention to exon-skipping. Relative intron strength to splicing inhibition correlates with the differential in GC content between adjacent introns and exons, leading to this differential global splicing pattern. We determine the crystal structure of human PHF5A and find that Y36 is located on the surface in a region of high sequence conservation. Structural analysis of the cryo-EM spliceosome Bact complex shows that these mutations cluster in a well-defined pocket surrounding the branch point adenosine suggesting a possible competitive mode of action for these splicing modulators, which interact with the aromatic side-chain of PHF5A-Y36. Collectively, we propose that PHF5A-SF3B1 forms a central node for binding to these small-molecule splicing modulators, offering insights to modulate splicing.

2017-05-25 | GSE96917 | GEO

Decreased serine biosynthesis identifies a subgroup of platinum resistant ovarian cancers and novel actionable metabolic vulnerabilities

Project description:Decreased serine biosynthesis identifies a subgroup of platinum resistant ovarian cancers and novel actionable metabolic vulnerabilities

| PRJNA735397 | ENA

RNA-seq analysis of shCTR and shSF3B1 NHD13-derived HSPC (cKIT+) cells

Project description:SF3B1 is the most mutated splicing factor (SF) in myelodysplastic syndromes (MDS), clonal hematopoietic disorders with variable risk of leukemic transformation. Although the tumorigenic effects of SF3B1 mutations have been defined, the role of “non-mutated” SF3B1 in cancer remains largely unresolved. Here we identify a conserved epitranscriptomic program that steers SF3B1 translation to counteract leukemogenesis. Our analysis of human and murine pre-leukemic MDS cells reveals a remarkable SF3B1 protein increase. Selective inhibition of SF3B1 upregulation accelerates MDS-to-leukemia progression in vivo. Mechanistically, ALKBH5-driven m6A demethylation within the SF3B1 5’ UTR fine-tunes SF3B1 translation to direct splicing of central DNA repair and epigenetic regulators during transformation. Loss of 5’ UTR m6A increases SF3B1 abundance, genome stability and delays leukemia progression in vivo, supporting integrative analysis of SF3B1 molecular signatures in humans that may predict tumor mutational burden and poor prognosis. These findings highlight a post-transcriptional gene expression nexus that unveils unanticipated SF3B1-dependent cancer vulnerabilities.

2023-03-21 | GSE198464 | GEO

RNA-seq analysis in fibroblast IMR90 CTRL/MYC/MYC+SF3B1 KD

2023-03-21 | GSE189585 | GEO

RNA-seq analysis in SF3B1 5’UTR WT and A88G MOLM-13 cells

2023-03-21 | GSE189584 | GEO