Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of PRMT5 as a therapeutic target in cholangiocarcinoma [RNA-seq I]

ABSTRACT: Cholangiocarcinoma is a very aggressive cancer whose incidence is increasing. Moreover, chemotherapies are little effective and the response to immune checkpoint inhibitors is low. We have identified protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in cholangiocarcinoma. PRMT5-targeting drugs markedly inhibited CCA cells proliferation, synergizing with cisplatin and gemcitabine, and hindered the growth of cholangiocarcinoma organoids. PRMT5 inhibition blunted the expression of oncogenic genes involved in chromatin remodeling and DNA repair, consistently inducing the formation of RNA-loops and promoting DNA damage. Our findings support the evaluation of PRMT5 inhibitors in clinical trials.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270017 | GEO | 2025/06/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of PRMT5 as a therapeutic target in cholangiocarcinoma [RNA-seq II]

Project description:Cholangiocarcinoma is a very aggressive cancer whose incidence is increasing. Moreover, chemotherapies are little effective and the response to immune checkpoint inhibitors is low. We have identified protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in cholangiocarcinoma. Treatment with PRMT5 inhibitor significantly restrains the growth of experimental cholangiocarcinoma model TAZ/AKT without adverse effects. Our findings support the evaluation of PRMT5 inhibitors in clinical trials.

2025-06-17 | GSE270181 | GEO

The therapeutic effect of KSP inhibitors in preclinical models of cholangiocarcinoma

Project description:Cholangiocarcinoma (CCA) is an epithelial malignancy with a dismal prognosis owing to limited treatment options. Here, we identified several compound candidates against CCA using a high-throughput drug screen with approved or emerging oncology drugs, among which kinesin spindle protein (KSP) inhibitors showed potent cytotoxic effects on CCA cells. Treatment with KSP inhibitors SB743921 and ARRY520 caused significant tumor suppression in CCA xenograft models in vivo. Mechanistically, KSP inhibitors led to the formation of abnormal monopolar spindles, which further resulted in the mitotic arrest and cell death of CCA cells both in vivo and in vitro. KEGG pathway analysis of transcriptional data confirmed this finding. Moreover, our clinical data as well as the TCGA database showed KIF11 expression was abundant in most CCA tumor specimens and associated with poor outcomes of CCA patients. Our results demonstrate that the therapeutic regimen of KSP inhibitors could be a promising treatment strategy in CCA.

2022-09-28 | GSE212232 | GEO

PARP inhibitor augments anti-tumor efficacy of DNMT inhibitor in cholangiocarcinoma

Project description:Cholangiocarcinoma (CCA) is a dismal, heterogeneous malignancy with limited treatment options. One of the key epigenetic dysregulations in CCA is aberrant DNA methylation, suggesting that targeted DNA methylation is a promising therapeutic strategy for this disease. However, the clinical utility of DNA demethylation reagents is not well documented. Here, we established patient-derived CCA cell lines and demonstrated that the demethylating agents decitabine and 5-azacytidine had minimal effects on antitumor proliferation of CCA cells. A combinatorial drug screen using a kinase inhibitor library identified PARP inhibitors as sensitizers that synergistically enhanced the antitumor effects of decitabine. The combination of DNMT inhibitors and PARP inhibitors significantly blocks tumor growth in both CCA patient-derived xenograft models and the somatic CCA model induced by hydrodynamic tail vein injection. Transcriptomic profiling analysis showed that the combination treatment activated the inflammatory signaling pathway and upregulated senescence-associated secretory phenotype gene expression, resulting in genomic instability in CCA. Mechanistically, combination treatment disrupted XRCC1 function and increased PARP1 trapping, leading to persistent DNA damage and senescence. Together, our study provides a preclinical proof-of-concept for the use of DNMT inhibitors in combination with PARP inhibitors as a novel therapeutic strategy and potentially optimizes current clinical practice in the treatment of CCA.

2025-06-18 | GSE275134 | GEO

Human cholangiocarcinoma LC-MS/MS

Project description:The glycosylation landscape of Human cholangiocarcinoma (CCA), and how it affects CCA diagnosis and prognosis, has recently emerged as an appealing research field.In this study, we used chemical glycoproteomic analysis Click-iG for systematic profiling of intact glycopeptides in CCA and HIBEpiC cell lines.

2024-06-22 | PXD048188 | Pride

Serum exosome miRNA expression profile in patients with cholangiocarcinoma(CCA) and common bile duct stones(CBDS)

Project description:Cholangiocarcinoma (CCA) is a type of highly aggressive cancer arising from the biliary system. Through serum exosome miRNA sequencing, we screened out the differentially expressed miRNA in patients with cholangiocarcinoma(CCA) and common bile duct stones(CBDS).

2022-10-20 | GSE215448 | GEO

Next generation sequencing of human cholangiocarcinoma cells and associated stem-like component

Project description:The goal of this study is to provide a global transcriptome profiling (RNA-seq) of stem-like subset in human cholangiocarcinoma (CCA). Functional enrichment of CCA stem-like subset was performed by 3D sphere culture (SPH) in CCA cell lines. Comparison to parental CCA cells grown as 2D monolayer is provided.

2022-06-01 | GSE162845 | GEO

Identification of PRMT5 as a therapeutic target in cholangiocarcinoma

Project description:Identification of PRMT5 as a therapeutic target in cholangiocarcinoma

| PRJNA1125385 | ENA

mRNA and lncRNA expression in cholangiocarcinoma

Project description:Long noncoding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, associated with chronic inflammation and damage to the biliary epithelium. This study determined whether lncRNAs were dysregulated and participated in disease diagnosis or pivotal inflammation pathways through a genome-wide lncRNA screening and functional analysis. We firstly identified a large number of lncRNAs abnormally expressed between 9 pairs of cancerous and adjacent tissues of CCA, and between intra-hepatic CCA and extra-hepatic CCA through a genome-wide profiling. Our findings show that lncRNAs may be potential biomarkers of CCA progression.

2017-09-16 | GSE103909 | GEO

FOSL1 transcriptome in cholangiocarcinoma (CCA) cells

Project description:FOSL1 transcriptome in cholangiocarcinoma (CCA) cells

| PRJNA648046 | ENA

Chemotherapy response in cholangiocarcinoma

Project description:CCLP cholangiocarcinoma cells were transfected with CTRL inhibitor or MIR1249 inhibitor for 48 hours and treated with DMSO or chemotherapy (cisplatin and gemcitabine) for 48 hours before being collected and analysed for gene expression

2022-06-06 | GSE132328 | 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