Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting EZH2 increases the vulnerability of triple-negative breast cancer

ABSTRACT: Targeting EZH2 increases the vulnerability of triple-negative breast cancer

PROVIDER: PRJNA445854 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6903490.fastq.gz	Fastqsanger.gz
	SRR6903491.fastq.gz	Fastqsanger.gz
	SRR6903492.fastq.gz	Fastqsanger.gz
	SRR6903493.fastq.gz	Fastqsanger.gz
	SRR6903494.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 10

Similar Datasets

Targeting EZH2 increases the vulnerability of triple-negative breast cancer

Project description:We hypothesize that knockdown or inhibition of the EZH2 results in decreased proliferation and tumorigenic potential of TNBC breast cancer cells

2019-01-18 | GSE112378 | GEO

Targeting the vulnerability of RB tumor suppressor loss in triple negative breast cancer

Project description:Targeting the vulnerability of RB tumor suppressor loss in triple negative breast cancer

| PRJNA428502 | ENA

IL-17A increases doxorubicin efficacy in triple negative breast cancer

Project description:IL-17A increases doxorubicin efficacy in triple negative breast cancer

| PRJNA846314 | ENA

Global altered gene expression in triple-negative breast cancer tumor samples treated with CDK2 and EZH2 inhibitors

Project description:Triple-negative breast cancer cell line SUM-149 xenograft mouse model was treated with CDK2 inhibitor (dinaciclib) and EZH2 inhibitor (EPZ6438) for 10 days to examine global transcriptome alternations by RNAseq. Expression levels of more than 801 and 741 gene were altered by CDK2 inhibitor and EZH2 inhibitor treatment, respectively.Among differential changed genes induced by CDK2 inhibitor and EZH2 inhibitor, we defined top 109 common up- and down-regulated gene sets in the inhibitor-treated tumors.

2019-06-05 | GSE132194 | GEO

MYC-Alarmin Axis as a Novel Therapeutic Vulnerability in Triple Negative Myeloproliferative Neoplasms

Project description:Despite advances in our understanding of the underlying genetic abnormalities in myelofibrosis (MF) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly in triple negative MF patients who lack mutations in the JAK2 kinase pathway. Here we report that MYC copy number gain (e.g., trisomy 8) is frequently identified in triple negative MF where MF development and progression rely on MYC-directed activation of S100A9, a Danger Associated Molecular Pattern (DAMP) protein that plays pivotal roles in inflammation. Notably, MYC-S100A9 axis underlies complex network of inflammatory signaling that involves various hematopoietic cell types in the bone marrow microenvironment. Accordingly, small molecules targeting the MYC-S100A9 pathway effectively ameliorated the MF phenotypes, highlighting MYC-alarmin axis as a novel therapeutic vulnerability in a subgroup of MF patients.

2024-04-29 | GSE240963 | GEO

MYC-Alarmin Axis as a Novel Therapeutic Vulnerability in Triple Negative Myeloproliferative Neoplasms

Project description:MYC-Alarmin Axis as a Novel Therapeutic Vulnerability in Triple Negative Myeloproliferative Neoplasms

| PRJNA1005951 | ENA

A chemical screen identifies PRMT5 as a therapeutic vulnerability for paclitaxel-resistant triple-negative breast cancer

Project description:Paclitaxel -resistant triple negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat. Using an epigenetic chemical probe screen, we uncover an acquired vulnerability of paclitaxel-resistant TNBC cells to protein arginine methyltransferases (PRMTs) inhibition. Analysis of cell lines and in-house clinical samples demonstrates that resistant cells evade paclitaxel killing through stabilizing mitotic chromatin assembly. Genetic or pharmacologic inhibition of PRMT5 alters RNA splicing, particularly intron retention of Aurora kinases B (AURKB), leading to a decrease in protein expression, and finally results in selective mitosis catastrophe in paclitaxel-resistant cells. These findings are fully recapitulated in a patient derived xenograft (PDX) model generated from a paclitaxel-resistant TNBC patient, providing the rationale for targeting PRMTs in paclitaxel-resistant TNBC.

2024-06-21 | GSE264630 | GEO

Targeting Histone Modification Crosstalk as a Therapeutic Strategy for EZH2-aberrant Solid Tumors

Project description:Mutations or aberrant upregulation of the histone methyltransferase EZH2 occur frequently in human cancers yet EZH2-targeted therapies have only shown very limited clinical benefits in hematological malignancies. We report here that upon EZH2 inhibition, MLL1 interacts with p300/CBP complex that directs H3K27me loss to gain of H3K27ac modification. This histone modification crosstalk leads to transcriptional reprogramming that restricts the therapeutic response to EZH2 inhibition. Concurrent inhibition of H3K27 methylation and acetylation results in transcriptional repression and growth dependency on the MAPK signaling pathway in a large cancer subset. In pre-clinical models encompassing a broad spectrum of EZH2-aberrant solid tumors, a combination of EZH2 and BRD4 inhibitors or a triple-combination including MAPK inhibition display robust efficacy with tolerable toxicity, in particular in liver and pancreatic cancers. Our results suggest an attractive precision treatment and patient stratification strategy for EZH2-aberrant tumors on the basis of intrinsic MLL1 expression and feedback MAPK activation.

2018-09-10 | PXD010842 |

IL-17A increases doxorubicin efficacy in triple negative breast cancer [bulk RNA-seq]

Project description:IL-17A increases doxorubicin efficacy in triple negative breast cancer [bulk RNA-seq]

| PRJNA846318 | ENA

Epigenetic Co-Deregulation of EZH2/TET1 is a Senescence-Countering, Actionable Vulnerability in Triple-Negative Breast Cancer.

Project description:Triple-negative breast cancer (TNBC) cells lack the expression of ER, PR and HER2. Thus, TNBC patients cannot benefit from hormone receptor-targeted therapy as non-TNBC patients, but can only receive chemotherapy as the systemic treatment and have a worse overall outcome. More effective therapeutic targets and combination therapy strategies are urgently needed to improve the treatment effectiveness. Methods: We analyzed the expression levels of EZH2 and TET1 in TCGA and our own breast cancer patient cohort, and tested their correlation with patient survival. We used TNBC and non-TNBC cell lines and mouse xenograft tumor model to unveil novel EZH2 targets and investigated the effect of EZH2 inhibition or TET1 overexpression in cell proliferation and viability of TNBC cells. Results: In TNBC cells, EZH2 decreases TET1 expression by H3K27me3 epigenetic regulation and subsequently suppresses anti-tumor p53 signaling pathway. Patients with high EZH2 and low TET1 presented the poorest survival outcome. Experimentally, targeting EZH2 in TNBC cells with specific inhibitor GSK343 or shRNA genetic approach could induce cell cycle arrest and senescence by elevating TET1 expression and p53 pathway activation. Using mouse xenograft model, we have tested a novel therapy strategy to combine GSK343 and chemotherapy drug Adriamycin and could show drastic and robust inhibition of TNBC tumor growth by synergistic induction of senescence and apoptosis. Conclusions: We postulate that the well-controlled dynamic pathway EZH2-H3K27me3-TET1 is a novel epigenetic co-regulator module and provide evidence regarding how to exploit it as a novel therapeutic target via its pivotal role in senescence and apoptosis control. Of clinical and therapeutic significance, the present study opens a new avenue for TNBC treatment by targeting the EZH2-H3K27me3-TET1 pathway that can modulate the epigenetic landscape.

| S-EPMC6376470 | biostudies-literature

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