Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide gene expression analysis in RAS-mutated cells with EZH2 inactivation

ABSTRACT: Genome-wide gene expression analysis in RAS-mutated cells with EZH2 inactivation

PROVIDER: PRJNA630966 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Genome-wide gene expression analysis in RAS-mutated cells with EZH2 inactivation

Project description:EZH2 was inactivated by shRNA in the RAS-mutated HL-60 acute myeloid leukemia cell line. RNA-seq genome wide expression profiling was used to screen for genes deregulated by EZH2 inactivation within this setting.

2023-05-07 | GSE150029 | GEO

Genome-wide analysis of tumor regression upon K-RAS inactivation

Project description:We performed expression profiling on micro-dissected lung tumors derived from a doxycycline-inducible K-RAS mouse model in order to gain mechanistic insight into K-RAS-mediated tumor maintenance. In this model, the tumors were induced with doxycycline for 11 weeks (in order to obtain lung tumors). At this point the doxycyline was withrawn from the food of the mice and consequently K-RAS inactivated. Thus, the genome-wide analysis was performed on tumors at timepoints 0, 24h and 48h after K-RAS inactivation. Total RNA obtained from mouse lung tumors at time 0 and 24h or 48h after K-RAS inactivation.

2012-09-06 | E-GEOD-40606 | biostudies-arrayexpress

Genome-wide analysis of tumor regression upon K-RAS inactivation

2012-09-06 | GSE40606 | GEO

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

Catalytic subunits switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells [RNA-seq]

Project description:The SWI/SNF chromatin remodeling complex is altered in ~20% of human cancers. ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is the most frequently mutated epigenetic regulator in human cancers. Inactivation of the SWI/SNF complex is synthetically lethal with inhibition of EZH2 activity. EZH2 inhibitors are entering clinical trials for specific tumor types with SWI/SNF mutations. However, mechanisms of de novo or acquired resistance to EZH2 inhibitors in cancers with inactivating SWI/SNF mutations are unknown. Here we show that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2 drives resistance to EZH2 inhibitors in ARID1A-mutated ovarian cancer cells.

2019-02-10 | GSE110449 | GEO

Catalytic subunits switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells [ChIP-seq]

2019-02-10 | GSE110448 | GEO

RAS Pathway–Mutated Chronic Myelomonocytic Leukemia at the Single Cell Level

Project description:RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Using single-cell, multi-omics technologies, we sought to dissect the biological mechanisms underlying the initiation and progression of RAS pathway–mutated CMML. We found that RAS pathway mutations induced the transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs), which underwent proliferation and monocytic differentiation in response to cell-intrinsic and -extrinsic inflammatory signaling that also impaired immune cells’ functions. HSPCs expanded at disease progression and relied on the NF-KB pathway effector MCL1 to maintain their survival, which explains why patients with RAS pathway–mutated CMML do not benefit from BCL2 inhibitors such as venetoclax. Our study has implications for developing therapies to improve the survival of patients with RAS pathway–mutated CMML.

2024-04-21 | GSE218390 | GEO

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

2015-01-20 | GSE54979 | GEO

Transcriptome analysis for KDM6A mutated urothelial bladder carcinoma and EZH2 inhibitor treated KDM6A mutated urothelial bladder carcinoma

Project description:Purpose: The goals of this study are to compare 1. The transcription profile in KDM6A wildtype and KDM6A mutated urothelial bladder carcinoma. 2. The transcriptional changes in KDM6A mutated urothelial bladder carcinoma upon EZH2 inhibitor treatment.

2017-03-01 | GSE92723 | GEO

Inhibition of EGFR signaling downregulates K-RAS mutated activity

Project description:Inhibition of EGFR signaling downregulates K-RAS mutated activity

| PRJNA450257 | ENA