Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Small molecule RNA therapeutics to target prostate cancer [Ribo-seq]

ABSTRACT: Small molecule RNA therapeutics to target prostate cancer [Ribo-seq]

PROVIDER: PRJNA1193670 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR31592100.fastq.gz	Fastqsanger.gz
	SRR31592101.fastq.gz	Fastqsanger.gz
	SRR31592102.fastq.gz	Fastqsanger.gz
	SRR31592103.fastq.gz	Fastqsanger.gz
	SRR31592104.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Small molecule RNA therapeutics to target prostate cancer [RNA-seq]

Project description:Small molecule RNA therapeutics to target prostate cancer [RNA-seq]

| PRJNA1193667 | ENA

Small molecule RNA therapeutics to target prostate cancer [DMS MaP-seq]

Project description:Small molecule RNA therapeutics to target prostate cancer [DMS MaP-seq]

| PRJNA1193668 | ENA

Small molecule RNA therapeutics to target prostate cancer [Ribo-seq]

Project description:Tuning protein expression by targeting RNA structure using small molecules is an unexplored avenue for cancer treatment. To understand whether this vulnerability could be therapeutically targeted in the most lethal form of prostate cancer, castrate-resistant prostate cancer (CRPC), we used a clinical small molecule, zotatifin, that targets the RNA helicase and translation factor eIF4A. Zotatifin repressed tumorigenesis in patient-derived and xenograft models and prolonged survival in vivo alongside hormone therapy. Genome-wide transcriptome, translatome, and proteomic analysis revealed two important translational targets: Androgen Receptor (AR), a key oncogene in CRPC, and hypoxia-inducible factor 1A (HIF1A), an essential cancer modulator in hypoxia. We solved the structure of the 5’UTRs of these oncogenic mRNAs and strikingly observed complex structural remodeling of these select mRNAs by this small molecule. Remarkably, tumors treated with zotatifin become more sensitive to radiotherapy, usually blunted by HIF1A. Therefore, ‘translatome therapy’ opens new avenues to treat the deadliest cancers.

2025-02-16 | GSE283445 | GEO

Small molecule RNA therapeutics to target prostate cancer [RNA-seq]

2025-02-16 | GSE283446 | GEO

Small molecule RNA therapeutics to target prostate cancer [DMS MaP-seq]

2025-02-16 | GSE283444 | GEO

A small molecule BAG1 inhibitor as therapeutic agent for androgen receptor positive prostate cancer

Project description:BAG1 is a family of polypeptides with a conserved C-terminal BAG domain that functions as a nucleotide exchange factor for the molecular chaperone HSP70. BAG1 proteins also bind to diverse cellular proteins and control several signaling processes including proteostasis, apoptosis and transcription. The largest BAG1 isoform (BAG1L) controls the activity of the androgen receptor and is upregulated in prostate cancer. Here, we show that BAG1L binds to the AR N-terminal domain (NTD) and regulates AR dynamics and the expression of AR target genes. We further show that disruption of the BAG1L-AR NTD action by targeting the BAG domain with a small molecule, 2-(4-fluorophenyl)-5-(trifluoromethyl)-1,3-benzothiazole (A4B17), downregulates AR target gene expression and blocks proliferation of AR-positive prostate cancer cells. A4B17 also inhibits tumor development in mouse xenograft models under castration conditions. A4B17 is therefore a BAG1 inhibitor with unique properties to inhibit prostate cancer growth.

2022-05-05 | GSE182278 | GEO

Modulation of PSF binding property at RNA level by small molecule treatment in prostate cancer

Project description:Prostate cancer is the most common cancer in men and androgen receptor (AR) downstream signalings promote prostate cancer cell proliferation. PSF is a RNA binding protein which is involved in AR signaling.To investigate the effect of samll molecule, No.10-3, on the RNA binding ability of PSF, we performed RNA immunoprecipitation (RIP) sequence analysis in AR positive prostate cancer cell line long term androgen deprivation (LTAD) cells to explore the differences of PSF function to associate with RNAs in prostate cancer cells.

2021-05-01 | GSE169139 | GEO

Bypassing drug-resistance mechanisms of prostate cancer with small-molecules that target androgen receptor chromatin interactions

Project description:Human androgen receptor (AR) is a hormone-activated transcription factor that is an important drug-target in the treatment of prostate cancer. Current small molecule AR-antagonists (such as Enzalutamide) compete with male hormones that bind to the steroid binding pocket of the AR ligand binding domain (LBD). In castration-resistant prostate cancer (CRPC), drug-resistance can manifest through AR-LBD mutations that convert AR-antagonists into agonists, or by expression of AR-variants lacking the LBD. Such treatment resistance underscores the importance of novel ways of targeting the AR. In this study, we tested whether VPC14449, a small molecule inhibitor that was rationally designed to selectively target the AR DNA binding domain (DBD), could directly interfere with AR-DNA interactions. Using ChIP-seq in cell line models expressing AR or AR variants, we found that genome-wide chromatin binding of AR was dramatically impacted by VPC14449 (although with lesser effect on AR variants).

2018-02-16 | GSE96084 | GEO

Partitioning of cancer therapeutics in nuclear condensates

Project description:The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here we consider whether condensates concentrate small molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to impact the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy.

2020-04-27 | GSE149085 | GEO

PRC2 molecule EED is a target of epigenetic therapy of neuroblastoma

Project description:PRC2 molecule EED is a target of epigenetic therapy of neuroblastoma

| PRJNA760445 | ENA