Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Retinoids and EZH2 inhibitors cooperate to orchestrate cytotoxic effects on bladder cancer cells

ABSTRACT: Emerging evidence has highlighted the importance of targeting EZH2 in bladder cancer owing to the highly mutated nature of bladder cancers harboring mutations in chromatin regulatory genes opposing Polycomb-mediated repression, with enhanced expression of EZH2 contributing to pathogenesis. Here we report that coordinated targeting of EZH2 and the retinoic acid signaling pathway caused the cytotoxic effects on bladder cancer cells by inducing a synergistic reduction in proliferative potential that was associated with increased apoptosis and cell cycle arrest in a cooperative manner. Moreover, combined treatment caused the modulation of the expression of certain genes towards an anti-oncogenic profile, as reflected by the stimulation of marker genes associated with apoptosis and differentiation. To investigate the effects on gene regulatory networks associated with fenretinide and GSK-126 treatments at a genome-wide scale, we performed gene expression profiling analysis using data obtained from RNA-seq of T24 cells. We further portrayed a molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression of certain genes associated with unfolded protein response and some metabolic processes. This work also characterized an apoptotic program centered on the master transcriptional regulators C/EBPβ and CHOP. Our findings encourage the design of novel treatments employing retinoids coupled with EZH2 inhibitors in bladder carcinoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE229015 | GEO | 2024/01/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Retinoids and EZH2 inhibitors cooperate to orchestrate cytotoxic effects on bladder cancer cells

Project description:Retinoids and EZH2 inhibitors cooperate to orchestrate cytotoxic effects on bladder cancer cells

| PRJNA952561 | ENA

In vivo disruption of Rb-E2F-Ezh2 signaling loop causes bladder cancer development

Project description:Bladder cancer (BC) is a highly prevalent human disease in which Rb pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here we show that the in vivo inactivation of all Rb family genes in the mouse urothelium is sufficient to initiate BC development. The characterization of the mouse tumors revealed multiple molecular features of human BC, including the activation of E2F transcription factor and subsequent Ezh2 expression, and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. Whole transcriptional characterizations of the mouse bladder tumors revealed a significant overlap with human BC samples, and a predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, we determined that in human superficial BC patients, the increased tumor recurrence and progression in these recurrences is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial BC and demonstrate the existence of an Rb-E2F-Ezh2 axis in bladder whose disruption can promote tumor development. Gene expression was analyzed in normal bladder and bladder tumours, both in humans and in transgenic mice.

2014-10-02 | E-GEOD-38264 | biostudies-arrayexpress

Retinoic acid pathway activity in Wilms tumors and characterization of biological responses in vitro

Project description:Wilms tumor (WT) is one of the most common malignancies in childhood. With current therapy protocols up to 90 % of patients can be cured, but there is still a need to improve therapy for patients with aggressive WT and to reduce treatment intensity where possible. Prior data suggested deregulation of the retinoic acid (RA) pathway in high-risk WT. This could be validated in a large independent tumor set. Reduced RA pathway activity and MYCN overexpression were found in high risk tumors as opposed to tumors with low/intermediate risk, suggesting a beneficial impact of RA on advanced WT. To investigate the possible mode of action of retinoids as a novel therapeutic agent we treated primary tumor cell cultures with all-trans-RA (ATRA), 9cis-RA, fenretinide and combinations of retinoids and a histone deacetylase (HDAC) inhibitor. Genes deregulated in high risk tumors showed opposite changes upon treatment suggesting a positive effect of retinoids. 6/7 primary cultures tested reduced proliferation, irrespective of prior RA signaling levels. The only variant culture was derived from mesoblastic nephroma, a distinct childhood kidney neoplasm. Retinoid / HDAC inhibitor combinations provided no synergistic effect. ATRA and 9cis-RA induced morphological changes suggestive of differentiation, while fenretinide induced apoptosis in several cultures tested. Microarray analysis of ATRA treated WT cells revealed differential expression of many genes involved in extracellular matrix formation and osteogenic, neuronal or muscle differentiation. Although some of the effects appear to be reversible, these findings provide further evidence of a potential utility of retinoids in Wilms tumor treatment. total samples analysed are 2

2012-04-20 | E-GEOD-28807 | biostudies-arrayexpress

Role of Retinoids x Receptor and Retinoic Acid Receptor in Mouse Liver

Project description:Genome-wide binding of Retinoids x Receptor and Retinoic Acid Receptor in mouse liver was described

2013-05-15 | GSE46762 | GEO

Role of Retinoids x Receptor in Mouse Liver

Project description:Genome-wide binding of Retinoids x Receptor in mouse liver was described Using ChIP-Seq data to clarify the role of RXRa in liver

2013-05-15 | E-GEOD-46762 | biostudies-arrayexpress

Retinoic acid pathway activity in Wilms tumors and characterization of biological responses in vitro

2012-04-21 | GSE28807 | GEO

Regulation of uveal melanoma gene expression by retinoids

Project description:Regulation of uveal melanoma gene expression by retinoids

| PRJNA628695 | ENA

Effects of retinoids on estrogen-receptor-positive and -negative breast carcinoma cells: mRNA and miRNA profiling

Project description:This SuperSeries is composed of the following subset Series: GSE18390: Effects of retinoids on estrogen-receptor-positive and -negative breast carcinoma cells: mRNA profiling GSE18628: MicroRNA profiling shows different response to retinoids in estrogen-receptor positive and negative cells Refer to individual Series

2010-05-21 | E-GEOD-18693 | biostudies-arrayexpress

Transcriptional profile of human breast cancer MCF7 cells and clones thereof expressing human ERβ1 or ERβ2 upon treatment with antiestrogens and retinoids.

Project description:The aim of the experiment was to gain insight into the role of estrogen receptor beta (ERβ) isoforms in the response of breast cancer MCF7 cells to antiestrogens and retinoids. To this end, clones of MCF7 cells constitutively expressing human ERβ1 (MCF7-ERβ1) or ERβ2 (MCF7-ERβ2) were established and used for the determination of the global transcriptional changes induced upon treatment with hydroxytamoxifen (OHT) and all-trans retinoic acid (ATRA). Gene signatures associated with each clone will shed light to the mechanism underlying the ERβ1- and ERβ2-mediated response of MCF7 cells to antiestrogens and retinoids.

2022-12-13 | E-MTAB-12549 | biostudies-arrayexpress

In vivo disruption of Rb-E2F-Ezh2 signaling loop causes bladder cancer development

2014-10-02 | GSE38264 | GEO