EZH2 deficiency induced gene expression change in CRCs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE159352 | GEO | 2021/05/01
REPOSITORIES: GEO
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Project description:To identify genes whose expression was suppressed by EZH2, we performed gene expression microarray analysis in control and EZH2 knockdown human SKOV3 EOC cells. Two individual short hairpin RNAs to the human EZH2 gene (shEZH2) were used to limit potential off-target effects. Two individual short hairpin RNAs to the human EZH2 gene (shEZH2) were used to limit potential off-target effects. Three technical replicates per group were used.
2011-12-12 | E-GEOD-31433 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE40970: ChIP-seq analysis of H3K27me3 histone modification in EZH2 mutant and wild type DLBCL cell lines GSE40971: Gene expression profiling of EZH2 mutant and wild type DLBCL cell lines treated with EZH2 inhibitor GSE41239: Gene expression profiling of two DLBCL cell lines upon shRNA mediated knockdown of EZH2 Refer to individual Series
2012-10-12 | E-GEOD-40972 | biostudies-arrayexpress
Project description:To identify genes whose expression was suppressed by EZH2, we performed gene expression microarray analysis in control and EZH2 knockdown human SKOV3 EOC cells. Two individual short hairpin RNAs to the human EZH2 gene (shEZH2) were used to limit potential off-target effects.
2011-12-12 | GSE31433 | GEO
Project description:EZH2 deficiency induced gene expression change in CRCs
| PRJNA668530 | ENA
Project description:To detect the biological function of LncRNA GMDS-AS1 in colorectal cancer tumorigenesis, we constructed lentivirus-infected stable GMDS-AS1-knockdown (KD) HCT116 cell lines using shRNA (GMDS-AS1 shRNA2) and a nontarget control shRNA Next we performed gene expression profiling analysis using data obtained from RNA-seq of control and GMDS-AS1 KD cells, three biological replicates were applied.
2022-06-10 | GSE205630 | GEO
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
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
Project description:We studied transcriptional changes by Affymetrix human microarrays in 2 DLBCL cell lines as a result of shRNA mediated knockdown of EZH2. In eukaryotes, epigenetic post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is responsible for repressing target gene expression through methylation of histone H3 on lysine 27 (H3K27). Over-expression of EZH2 is implicated in tumorigenesis and correlates with poor prognosis in multiple tumor types. Recent reports have identified somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The Y641 residue is the most frequently mutated residue, with 22% of GCB (Germinal Cell B-cell) DLBCL and FL harboring mutations at this site. These lymphomas exhibit increased H3K27 tri-methylation (H3K27me3) due to altered substrate preferences of the mutant enzymes. However, it is unknown whether direct inhibition of EZH2 methyltransferase activity alone will be effective in treating lymphomas carrying activating EZH2 mutations. Herein, we demonstrate that GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and dramatically inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma. Pfeiffer and KARPAS-422 cells were treated with either shRNA targeting EZH2 (shEZH2) or a non targeting control (shNTC) for 10 days.
2012-10-12 | E-GEOD-41239 | biostudies-arrayexpress
Project description:Sprouty proteins are evolutionarily conserved modulators of mitogen-activated protein kinase pathway. Sprouty2 appears to function as a tumor suppressor in cancers, whereas we reported earlier that Sprouty2 functions as an oncogene in colorectal cancer. To further understand the oncogenic potential of Sprouty2 in the colon, microRNA expression profile of colon cancer cells was investigated. Sprouty2 suppression in HCT116 colon cancer cells significantly increased MicroRNA 194-5p. Sprouty2 dependent regulation of microRNA194-5p and its biological targets were studied further for their tumor suppressive actions in reducing epithelial-mesenchymal transition in colorectal cancer. Sprouty2 knockdown was performed by infecting HCT116 cells with three different lentivirus expressing shRNAs against human Sprouty2 mRNA and a control non targeted non-silencing shRNA (Sprouty2 MISSION shRNA Lentiviral Transduction Particles; TRCN 0000007522, TRCN 0000231589, TRCN 0000231588 and a non-targeted shRNA control from Sigma) following lentiviral transduction protocols provided by Sigma. Due to the random integration of the lentivirus into the host genome, varying levels of Sprouty2 gene knockdown was expected in puromycin resistant colonies. Three colonies in triplicate that demonstrated highest to lowest level of Sprouty2 suppression, as assessed by western blotting, were selected. RNA samples from these colonies and one from non-targeted shRNA expressing colony were prepared for microRNA expression profile analysis. Pooled RNA samples from each group were shipped to Exiqon for microRNA profiling based on miRCURY LNATM array technology.
2015-06-09 | E-GEOD-69665 | biostudies-arrayexpress
Project description:The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported. A Kaplan-Meier analysis on the event free- and overall survival of NB patients indicated that the highexpression of EZH2 correlated with an unfavorable prognosis. In order to elucidate the functional roles of EZH2 in NB tumorigenesis and its aggressiveness, we knocked down EZH2 in NB cell lines using lentivirus systems. The knockdown of EZH2 significantly induced NB cell differentiation, e.g. neurite extension, and the neuronal differentiation markers, NF68 and GAP43. EZH2 inhibitors also induced NB cell differentiation. We performed a comprehensive transcriptome analysis using Human Gene Expression Microarrays and found that NTRK1 (TrkA) is one of the EZH2-related suppression targets. The depletion of NTRK1 canceled EZH2 knockdown-induced NB cell differentiation. Our integrative methylome, transcriptome, and chromatin immunoprecipitation assays using NB cell lines and clinical samples clarified that the NTRK1 P1 and P2 promoter regions were regulated differently by DNA methylation and EZH2-related histone modifications. The NTRK1 transcript variants 1/2, which were regulated by EZH2-related H3K27me3 modifications at the P1 promoter region, were strongly expressed in favorable, but not unfavorable NB. The depletion and inhibition of EZH2 successfully induced NTRK1 transcripts and functional proteins. Collectively, these results indicate that EZH2 plays important roles in preventing the differentiation of NB cells and also that EZH2-related NTRK1 transcriptional regulation may be the key pathway for NB cell differentiation.
2018-05-01 | GSE98642 | GEO