Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Polycomb Group protein EZH2-mediated transcriptional repression of microRNA-338/-421 drives SPINK1-positive prostate cancer

ABSTRACT: Polycomb Group protein EZH2-mediated transcriptional repression of microRNA-338/-421 drives SPINK1-positive prostate cancer

PROVIDER: PRJNA427683 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Polycomb Group protein EZH2-mediated transcriptional repression of microRNA-338/-421 drives SPINK1-positive prostate cancer

Project description:SPINK1 overexpression defines the second largest subtype of prostate cancer (PCa), however molecular mechanisms underlying its upregulation remains poorly understood. Here, we identified the role of miR-338-5p and miR-421 in post-transcriptional regulation of SPINK1. We established that miR-338-5p/miR-421 mediates several cellular responses against SPINK1-positive cancer by targeting oncogenic long non-coding RNA (lncRNA) MALAT1, inducing cell-cycle arrest, inhibiting epithelial-to-mesenchymal transition (EMT), cancer-stemness and drug resistance. Moreover, ectopic expression of miR-338-5p/miR-421 abrogates SPINK1-mediated oncogenesis, tumor growth and distant metastases in murine model. Importantly, RNA-sequencing expression analysis revealed an inverse correlation between miRNAs and SPINK1 or MALAT1 in PCa patients’ specimens. Further, we demonstrate Polycomb group protein EZH2-mediated epigenetic silencing of miR-338-5p/miR-421 in SPINK1-positive subtype. Thus, restoring miR-338-5p/miR-421 expression using epigenetic drugs or synthetic mimics could abrogate SPINK1-mediated oncogenesis by targeting multiple oncogenic pathways and eliciting anti-cancer pleiotropic effects. Taken together, the present study unravels the molecular mechanism underlying SPINK1 overexpression and suggests miR-338-5p and miR-421 replacement therapy for the treatment of SPINK1-positive malignancies.

2018-12-30 | GSE108558 | GEO

Affinify Purification of EZH2 and phosphodeficient EZH2 identifies phosphorylation dependent interactions of EZH2

Project description:Overexpression of EZH2 in estrogen receptor negative (ER-) breast cancer promotes metastasis. EZH2 has been mainly studied as the catalytic component of the Polycomb Repressive Complex 2 (PRC2) that mediates gene repression by trimethylating histone H3 at lysine 27 (H3K27me3). However, how EZH2 drives metastasis despite the low H3K27me3 levels observed in ER- breast cancer is unknown. We have shown that in human invasive carcinomas and distant metastases, cytoplasmic EZH2 phosphorylated at T367 is significantly associated with ER- disease and low H3K27me3 levels. Here, we explore the interactome of EZH2 and of a phosphodeficient mutant EZH2_T367A. We identified novel interactors of EZH2, and identified interactions that are dependent on the phosphorylation and cellular localization of EZH2 that may play a role in EZH2 dependent metastatic progression.

2018-07-03 | PXD010073 | Pride

UI-421

Project description:UI-421

| PRJEB28041 | ENA

Effects of T350 phospho- on gene repression activity of EZH2

Project description:The Polycomb group (PcG) protein enhancer of zeste homolog 2 (EZH2) plays an essential role in histone methylation-mediated epigenetic gene silencing. We demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and 2 (CDK2) bind to and phosphorylate EZH2 at threonine 350 (T350) in an evolutionally conserved motif. T350 phosphorylation is required for EZH2 function in silencing of genes that promote differentiation and inhibit proliferation and migration. Blockage of T350 phosphorylation by generating a T350A mutation largely diminishes the global effect of EZH2 on gene silencing. Seven experiments have been designed. LNCaP cells were transfected with si-Control, si-EZH2, si-EZH2 plus RNAi resistant EZH2 plasmid, or si-EZH2 plus RNAi resistant T350A mutated EZH2 plsamid for 60 hours, or treated with DMSO, 5 uM TSA, or 10 uM Roscovitine for 24 hours. Two replicates per experiment.

2010-11-02 | E-GEOD-20433 | biostudies-arrayexpress

Effect of T350 phosphorylation on gene repression activity of EZH2 in BJ cells

Project description:The Polycomb group (PcG) protein enhancer of zeste homolog 2 (EZH2) plays an essential role in histone methylation-mediated epigenetic gene silencing. We demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and 2 (CDK2) bind to and phosphorylate EZH2 at threonine 350 (T350) in an evolutionally conserved motif. T350 phosphorylation is required for EZH2 function in silencing of genes that promote differentiation and inhibit proliferation and migration. Blockage of T350 phosphorylation by generating a T350A mutation largely diminishes the global effect of EZH2 on gene silencing. Four experiments have been designed. BJ cells were transfected with si-Control, si-EZH2, si-EZH2 plus RNAi resistant lentivirus expressed EZH2, or si-EZH2 plus RNAi resistant lentivirus expressed T350A mutant for 60 hours. Each experiment was triplicated.

2010-11-10 | E-GEOD-22427 | biostudies-arrayexpress

Antihistamine Drug Ebastine inhibits cancer growth by targeting Polycomb Group Protein EZH2

Project description:Antihistamine Drug Ebastine inhibits cancer growth by targeting Polycomb Group Protein EZH2

2020-07-02 | GSE153652 | GEO

Polycomb Group Proteins EZH2 and EED Directly Regulate Androgen Receptor in Advanced Prostate Cancer

Project description:Polycomb group proteins are important epigenetic regulators for organ development, cell proliferation and differentiation, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including EZH2, promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. The canonical function of EZH2, along with its essential binding partners EED and SUZ12, is to methylate histone H3K27 and repress its downstream targets. In this study, we discover that EZH2 regulates androgen receptor (AR) expression levels and AR signaling in prostate cancer. Targeting EZH2 with the newly identified EZH2 inhibitor, astemizole, could effectively inhibit the progression of castration-resistant prostate cancer.

2018-12-22 | GSE124268 | GEO

Effects of T350 phospho- on gene repression activity of EZH2

2010-11-02 | GSE20433 | GEO

Escherichia coli strain:3-338 | isolate:3-338

Project description:Escherichia coli strain:3-338 | isolate:3-338 Genome sequencing

| PRJNA993437 | ENA

Sinorhizobium meliloti strain:421

Project description:Sinorhizobium meliloti 421 Resequencing

| PRJNA501540 | ENA