Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma drives human dilated cardiomyopathy

ABSTRACT: BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma drives human dilated cardiomyopathy

PROVIDER: PRJNA924277 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma drives human dilated cardiomyopathy

Project description:By using a small molecule compound library targeting epigenetic enzymes we have identified BRD9 enzyme for eliminating CSCs. Genomic and proteomic studies revealed that BRD9/BAF complex regulates expression of stemness factors and chemoresistance by cooperating with TGFβ/Activin-SMAD2/3 signalling pathway. Chemical inhibition and genetic loss of function of BDR9 blocks the self-renewal of CSCs, reduces CSC invasiveness and resensitizes PDAC CSCs to conventional therapies. Analyses of chromatin architecture showed that BRD9 regulates the 3D chromatin looping between promoters and enhancers of stemness genes and EMT regulators in CSCs. BRD9 inhibition abrogated tumour formation in mice and eliminated CSCs in tumours from pancreatic cancer patients. Collectively, we uncovered BRD9 enzyme as an attractive therapeutic target for re-sensitizing and eliminating CSCs in pancreatic cancer patients.

2024-01-01 | GSE222952 | GEO

BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma.

Project description:Background & aimsThe dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence of pancreatic cancer stem-like cells (CSCs) that respond poorly to current chemotherapy regimens. The epigenetic mechanisms regulating CSCs are currently insufficiently understood, which hampers the development of novel strategies for eliminating CSCs.MethodsBy small molecule compound screening targeting 142 epigenetic enzymes, we identified that bromodomain-containing protein BRD9, a component of the BAF histone remodeling complex, is a key chromatin regulator to orchestrate the stemness of pancreatic CSCs via cooperating with the TGFβ/Activin-SMAD2/3 signaling pathway.ResultsInhibition and genetic ablation of BRD9 block the self-renewal, cell cycle entry into G0 phase and invasiveness of CSCs, and improve the sensitivity of CSCs to gemcitabine treatment. In addition, pharmacological inhibition of BRD9 significantly reduced the tumorigenesis in patient-derived xenografts mouse models and eliminated CSCs in tumors from pancreatic cancer patients. Mechanistically, inhibition of BRD9 disrupts enhancer-promoter looping and transcription of stemness genes in CSCs.ConclusionsCollectively, the data suggest BRD9 as a novel therapeutic target for PDAC treatment via modulation of CSC stemness.

| S-EPMC11304550 | biostudies-literature

Dilated Cardiomyopathy

Project description:Dilated Cardiomyopathy

| PRJNA1006418 | ENA

Dilated cardiomyopathy vs Myocarditis

Project description:Dilated cardiomyopathy vs Myocarditis

| PRJNA493608 | ENA

Dilated Cardiomyopathy in Dobermans and Boxers

Project description:This study attempts at investigating the changes in cardiac gene expression that occur in Dilated Cardiomyopathy (DCM). DCM in Dobermans and Boxers are the focus of this study. Control heart tissue as well as Pacing tissue used is from mongrel dogs. Keywords: control vs pacing vs disease; strain specific disease 3 Dobermans-DCM, 4 Boxers-DCM, 3 mongrels-control and 3 mongrels-pacing

2008-05-08 | E-GEOD-11015 | biostudies-arrayexpress

Cardiac fibroblasts of dilated cardiomyopathy patients

Project description:To investigate the physiological characteristics of cardiac fibroblasts (CF) from pediatric dilated cardiomyopathy (DCM) patients, CFs were harvested from left ventricular free wall at the heart transplantation. We then performed RNA-seq for 7 different lines of CFs.

2023-09-12 | GSE223517 | GEO

Dilated Cardiomyopathy in Dobermans and Boxers

2008-05-08 | GSE11015 | GEO

Dilated Cardiomyopathy and Non Failing Biopsies

Project description:Dilated cardiomyopathy (DCM) is a common cause of heart failure and a leading cause of cardiac transplantation in western countries. The robust predictive expression profile of cardiomyopathic and NF hearts as well as the functional classification can help to identify promising candidates for DCM and may improve the early diagnosis of cardiomyopathy. Keywords: disease state analysis

2006-08-01 | GSE3585 | GEO

Cardiac fibroblasts of dilated cardiomyopathy patients

Project description:Cardiac fibroblasts of dilated cardiomyopathy patients

| PRJNA926632 | ENA

Dilated Cardiomyopathy and Non Failing Septal Biopsies

2006-08-01 | GSE3586 | GEO