Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting TCA cycle through Cuproptosis confers Synthetic Lethality to ARID1A Deficiency Hepatocellular Carcinoma [ATAC-Seq]

ABSTRACT: Targeting TCA cycle through Cuproptosis confers Synthetic Lethality to ARID1A Deficiency Hepatocellular Carcinoma [ATAC-Seq]

PROVIDER: PRJNA948440 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23958391_1.fastq.gz	Fastqsanger.gz
	SRR23958391_2.fastq.gz	Fastqsanger.gz
	SRR23958392_1.fastq.gz	Fastqsanger.gz
	SRR23958392_2.fastq.gz	Fastqsanger.gz
	SRR23958393_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Targeting TCA cycle through Cuproptosis confers Synthetic Lethality to ARID1A Deficiency Hepatocellular Carcinoma

Project description:Targeting TCA cycle through Cuproptosis confers Synthetic Lethality to ARID1A Deficiency Hepatocellular Carcinoma

| PRJNA948437 | ENA

Targeting TCA cycle through Cuproptosis confers Synthetic Lethality to ARID1A Deficiency Hepatocellular Carcinoma [Cut&Run]

Project description:Targeting TCA cycle through Cuproptosis confers Synthetic Lethality to ARID1A Deficiency Hepatocellular Carcinoma [Cut&Run]

| PRJNA948438 | ENA

Targeting TCA cycle through Cuproptosis confers Synthetic Lethality to ARID1A Deficiency Hepatocellular Carcinoma [ATAC-Seq]

Project description:To further explore the mechanisms of glucose metabolic reprogramming in ARID1A deficiency HCC, we conducted multi-omics profilings in ARID1A deficient and wild type Hep3B cells.

2023-09-07 | GSE228176 | GEO

Targeting TCA cycle through Cuproptosis confers Synthetic Lethality to ARID1A Deficiency Hepatocellular Carcinoma [Cut&Run]

2023-09-07 | GSE228175 | GEO

Targeting TCA cycle through Cuproptosis confers Synthetic Lethality to ARID1A Deficiency Hepatocellular Carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-07 | GSE228179 | GEO

Dysregulated Wnt signaling confers resistance to cuproptosis in cancer cells

Project description:Cuproptosis is characterized by the aggregation of lipoylated components of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. Dysregulation of copper homeostasis and resulting cuproptosis induction is an emerging area of interest for cancer therapy. However, mechanisms of cancer cell evasion of cuproptosis are not well understood. Here, we found that the cuproptosis process is accompanied by activation of the Wnt/β-catenin pathway. Mechanistically, copper binds to PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/β-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/β-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed that the β-catenin/TCF4 transcriptional complex directly binds to the promoter region of ATP7B, a protein responsible for the efflux of copper ions from the cell, inducing its expression and reducing intracellular copper accumulation, thereby inhibiting cuproptosis. Knockdown of TCF4 or pharmacological blockade of the Wnt/β-catenin pathway increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/β-catenin pathway and cuproptosis sensitivity, and may provide a precision medicine strategy for cancer treatment by selectively inducing cuproptosis

2023-11-21 | GSE248083 | GEO

Dysregulated Wnt signaling confers resistance to cuproptosis in cancer stem cells

2023-11-21 | GSE248084 | GEO

PPP2R1A mutations cause ATR inhibitor synthetic lethality in ARID1A deficient ovarian clear cell carcinoma

Project description:Ovarian clear cell carcinoma (OCCC) is a cancer of unmet need characterized by ARID1A mutation. Prior work identified an ARID1A/ATR synthetic lethality, information that led to phase II clinical trials. Using genome-wide CRISPR-Cas9 mutagenesis and interference screens, we identified protein phosphatase 2A (PP2A) subunits, including PPP2R1A, as determinants of ATRi sensitivity in ARID1A mutant OCCC. Analysis of an OCCCs cohort indicated that >1/3 possessed both PPP2R1A and ARID1A loss-of-function mutations. CRISPR-prime editing demonstrated that oncogenic PPP2R1A p.R183 missense mutations enhance in vitro and in vivo ATRi sensitivity in ARID1A mutant OCCC. OCCC patients with both ARID1A and PPP2R1A mutations also showed clinical responses to ATRi in a phase II trial. Mechanistically, this synthetic lethal effect is dependent upon WNK1 kinase, which opposes PP2A function. This data suggests that co-occurrence of PPP2R1A and ARID1A mutations in OCCC should be assessed as a biomarker of ATRi response in on-going clinical trials.

2023-05-10 | PXD040422 | Pride

Targeting EZH2 methyltransferase activity in ARID1A mutated cells as a synthetic lethal therapeutic strategy

Project description:ARID1A, an epigentic modifier, is often mutated in ovarian clear cell carcinoma (OCCC). In addition, EZH2 is frequently upregulated in OCCC. Inhibtion of EZH2 with an inhibitor (GSK126) selectively inhibits ARID1A-mutated cells. This study was designed to understand changes in gene expression profiles following EZH2 inhibition or ARID1A restoration. Chromatin remodelers such as ARID1A are frequently mutated in a broad array of cancers. However, targeted cancer therapy based on ARID1A mutation status has not been described. Intriguingly, ARID1A mutated cancers typically lack genomic instability, suggesting significant involvement of epigenetic mechanisms. Here we show that inhibition of the EZH2 methyltransferase acts in a synthetic lethal manner in ARID1A mutated cells. Remarkably, ARID1A mutation status correlated with response to EZH2 inhibitor. Genome-wide profiling revealed antagonistic roles of ARID1A and EZH2 in gene regulation. Further, we identified PIK3IP1 as a direct ARID1A/EZH2 target gene whose upregulation contributes to the observed synthetic lethality in the EZH2 inhibitor treated ARID1A mutated cells. Significantly, EZH2 inhibitor caused the regression of established ARID1A mutated tumors in vivo. Together, this data demonstrate a synthetic lethality between ARID1A mutation and EZH2 inhibition. They indicate that pharmacological inhibition of EZH2 represents a novel treatment strategy for ARID1A mutated cancers.

2015-01-20 | E-GEOD-54979 | biostudies-arrayexpress

ARID1A KLF5 synthetic lethality CRISPR screen in U2OS cells

Project description:ARID1A KLF5 synthetic lethality CRISPR screen in U2OS cells

| PRJEB75512 | ENA