GSE222952 BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma drives human dilated cardiomyopathy

Contributors : Yuliang Feng ; Liuyang Cai ; Chao-Hui Chang ; Feng Liu ; Lei Jiang ; Siim PauklinSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBy 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 TGF β/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 betwe en 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 CS Cs in pancreatic cancer patients.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research