Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional responses of human melanoma cells to EZH2 inhibition

ABSTRACT: Transcriptional responses of human melanoma cells to EZH2 inhibition

PROVIDER: PRJNA589591 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional responses of human melanoma cells to EZH2 inhibition

Project description:The epigenetic modifier EZH2 is part of the polycomb repressive complex that suppresses gene expression via histone methylation. Activating mutations in EZH2 are found in a subset of melanoma that contributes to disease progression by inactivating tumor suppressor genes. In this study we have targeted EZH2 with a specific inhibitor (GSK126) or depleted EZH2 protein by stable shRNA knockdown. We show that inhibition of EZH2 has potent effects on the growth of both wild-type and EZH2 mutant human melanoma in vitro particularly in cell lines harboring the EZH2Y646 activating mutation. This was associated with cell cycle arrest, reduced proliferative capacity in both 2D and 3D culture systems, and induction of apoptosis. The latter was caspase independent and mediated by the release of apoptosis inducing factor (AIFM1) from mitochondria. Gene expression arrays showed that several well characterized tumor suppressor genes were reactivated by EZH2 inhibition. This included activating transcription factor 3 (ATF3) that was validated as an EZH2 target gene by ChIP-qPCR. These results emphasize a critical role for EZH2 in the proliferation and viability of melanoma and highlight the potential for targeted therapy against EZH2 in treatment of patients with melanoma. Tiffen JC, Gunatilake D, Gallagher SJ, Gowrishankar K, Heinemann A, Cullinane C, et al. Targeting activating mutations of EZH2 leads to potent cell growth inhibition in human melanoma by derepression of tumor suppressor genes. Oncotarget 2015;12:12

2019-11-15 | GSE140394 | GEO

Transcriptional responses of melanoma cells to BRAF inhibition

Project description:Transcriptional responses of melanoma cells to BRAF inhibition

| PRJNA432707 | ENA

Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status

Project description:Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status

2016-06-06 | GSE79905 | GEO

EZH2-mediated primary cilium deconstruction drives metastatic melanoma formation

Project description:Human melanomas frequently harbor amplifications of EZH2. However, the oncogenic contribution of this methyltransferase to melanoma formation has remained elusive. Taking advantage of murine melanoma models, we now show that EZH2 drives tumorigenesis from benign BrafV600E or NrasQ61K-expressing melanocytes. EZH2 oncogenicity results from silencing of genes relevant for the integrity of the primary cilium, a signaling organelle projecting from the surface of vertebrate cells. Consequently, gain of EZH2 function promotes loss of primary cilia in benign melanocytic lesions. In contrast, blockade of EZH2 activity evokes ciliogenesis and cilia-dependent growth inhibition in malignant melanoma. Finally, we demonstrate that loss of cilia enhances pro-tumorigenic WNT/β-catenin signaling and is itself sufficient to drive metastatic melanoma in benign cells. Thus, primary cilia deconstruction is a key process in EZH2-driven melanomagenesis.

2019-04-04 | GSE112677 | GEO

EZH2 gain-of-function mutations distort H3K27me3 landscapes and transform transcriptional responses to PRC2 inhibition.

Project description:EZH2 gain-of-function mutations distort H3K27me3 landscapes and transform transcriptional responses to PRC2 inhibition.

| PRJNA905334 | ENA

The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors

Project description:Increased activity of the epigenetic modifier EZH2 has been associated with different cancers. However, evidence for a functional role of EZH2 in tumourigenesis in vivo remains poor, in particular in metastasising solid cancers. Here we reveal central roles of EZH2 in promoting growth and metastasis of cutaneous melanoma. In a melanoma mouse model, conditional Ezh2 ablation as much as treatment with the preclinical Ezh2 inhibitor GSK503 stabilises the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology. Comparably, in human melanoma cells, EZH2 inactivation impairs proliferation and invasiveness, accompanied by re-expression of tumour suppressors connected to increased patient survival. These EZH2 target genes suppress melanoma growth and prevent EMT / metastasis in vivo revealing the dual function of EZH2 in promoting tumour progression. Thus, EZH2-mediated epigenetic repression is highly relevant especially during advanced melanomagenesis, which makes EZH2 a promising target for novel melanoma therapies.

2014-11-12 | GSE63165 | GEO

EZH2-dependent transcriptional complex promotes aberrant epithelial remodelling after injury

Project description:Unveiling the molecular mechanisms of tissue remodelling following injury is imperative to elucidate its regenerative capacity and aberrant repair in disease. Using different omics approaches, we identified enhancer of zester homolog 2 (EZH2) as a key regulator that initiates a fibrotic cascade in injured lung epithelium. Epithelial-injury-driven enrichment of nuclear transforming growth factor-b-activated kinase 1 (TAK1) mediates EZH2 phosphorylation to facilitate the release of EZH2 from polycomb repressive complex 2 (PRC2). This process leads to the establishment of a fibrotic transcriptional complex of EZH2, RNA-polymerase II (POL2) and nuclear actin, which orchestrates aberrant epithelial lung repair programs. The liberation of EZH2 from PRC2 is accompanied by an EZH2-EZH1 switch to preserve silencing at non-target genes. Loss of epithelial TAK1, EZH2 or blocking nuclear actin influx attenuates the fibrotic cascade and restores respiratory homeostasis. Accordingly, EZH2 inhibition significantly improves outcomes in a pulmonary fibrosis mouse model. Our results reveal an important non-canonical function of EZH2, paving the way for new therapeutic interventions in fibrotic lung diseases.

2021-04-27 | MSV000087321 | MassIVE

Cytosolic PRRs are required to upregulate interferon gene expression upon EZH2 inhibition with GSK343 in B16-F10 melanoma cells [RNA-seq]

Project description:EZH2 is a histone methyltransferase that deposits the repressive histone H3 lysine 27 trimethylation (H3K27me3). This mark has been reported to silence expression of various repetitive elements in the genome. We sought to identify the effect of EZH2 inhibition on coding and non-coding, repetitive RNA expression. We generated a novel mutant mouse line whose ability to detect induced repeat element expression has been abrogated. We report that the mutant splenic B cells fail to upregulate inflammatory gene expression upon EZH2 inhibition, despite comparable upregulation of various repetitive elements with WT. Unlike WT splenic B cells that do not upregulate interferon gene expression upon EZH2 inhibition, B16-F10 melanoma cells activate their expression under the same inhibitor treatment. Cytosolic pattern recognition receptors, RIG-I and Cgas, are required for such response as their deletion abrogates this pathway.

2023-10-18 | GSE239879 | GEO

EZH2 gain-of-function mutations distort H3K27me3 landscapes and transform transcriptional responses to PRC2 inhibition [RNA-seq]

Project description:EZH2 gain-of-function mutations distort H3K27me3 landscapes and transform transcriptional responses to PRC2 inhibition [RNA-seq]

| PRJNA905335 | ENA

Transcriptional responses of melanoma cells to BRAF inhibition

Project description:We performed a time-course experiment to determine the temporal transcriptional changes that occur in human melanoma cells when cultured with the BRAF inhibitor vemurafenib from 3 days to 73-90 days.

2018-06-07 | GSE110054 | 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