Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Downregulation of CBX7 induced by EZH2 upregulates FGFR3 expression to reduce sensitivity to cisplatin in bladder cancer

ABSTRACT: Cisplatin-based cytotoxic chemotherapy is considered to be the first-line therapy for advanced bladder cancer (BC), but resistance to cisplatin limits its antitumor effect. Fibroblast growth factor receptor 3 (FGFR3) has been reported to contribute to the progression and cisplatin resistance of BC. Meanwhile, chromobox protein homolog 7 (CBX7) was reported to inhibit BC progression. And our previous RNA-seq data on CBX7 (GSE185630) suggested that CBX7 might repress FGFR3，but the underlying mechanism and other cancer-related functions of CBX7 are still unknown.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214886 | GEO | 2025/10/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Downregulation of CBX7 induced by EZH2 upregulates FGFR3 expression to reduce sensitivity to cisplatin in bladder cancer

Project description:Downregulation of CBX7 induced by EZH2 upregulates FGFR3 expression to reduce sensitivity to cisplatin in bladder cancer

| PRJNA887467 | ENA

Downregulation of CBX7 induced by EZH2 upregulates FGFR3 expression to reduce sensitivity to cisplatin in bladder cancer.

Project description:BackgroundCisplatin-based cytotoxic chemotherapy is considered to be the first-line therapy for advanced bladder cancer (BC), but resistance to cisplatin limits its antitumor effect. Fibroblast growth factor receptor 3 (FGFR3) has been reported to contribute to the progression and cisplatin resistance of BC. Meanwhile, chromobox protein homologue 7 (CBX7) was reported to inhibit BC progression. And our previous RNA-seq data on CBX7 (GSE185630) suggested that CBX7 might repress FGFR3, but the underlying mechanism and other cancer-related functions of CBX7 are still unknown.MethodsSilico analysis of RNA-seq data to identify the upstream regulators and downstream target genes of CBX7. The western blot analysis, quantitative real-time PCR (RT-qPCR), chromatin immunoprecipitation (ChIP)-qPCR analysis, CCK-8 assay, and nude mice xenograft models were used to confirm the enhancer of zeste homologue (EZH2)/CBX7/ FGFR3 axis.ResultsIn this study, we first showed that CBX7 is downregulated in BC. Then, we revealed that EZH2 represses CBX7 expression by increasing H3K27me3 in BC cells. Moreover, we demonstrated that CBX7 directly downregulates FGFR3 expression and sensitises BC cells to cisplatin treatment by inactivating the phosphatidylinositol 3-kinase (PI3K)-(RAC-alpha serine/threonine-protein kinase) AKT signalling pathway.ConclusionsThese results suggest that CBX7 is an ideal candidate to overcome cisplatin resistance in BC.

| S-EPMC9902481 | biostudies-literature

CBX7 Promotes Lung Adenocarcinoma Metastasis by Transcriptionally Repressing SOCS3

Project description:In lung adenocarcinoma (LUAD), metastasis is a leading cause of mortality and notably tends to occur at an early stage of the disease. CBX7, a component of canonical Polycomb Repressive Complex 1 (PRC1) which mediates transcriptional repression, exhibits complex and context-dependent functions across different types of cancer. However, the roles of CBX7 in LUAD metastasis remain largely uncharacterized. Here we report that overexpression of CBX7 promotes, whereas its knockdown suppresses, LUAD cell migration and invasion in vitro. In vivo studies further confirm the pro-metastatic role of CBX7 in LUAD. Mechanistically, CBX7 suppresses the expression of SOCS3, which has been reported to be involved in cancer cell migration and invasion. At the molecular level, CBX7 binds to SOCS3 transcription start site (TSS) downstream region to establish monoubiquitination of histone H2A at lysine 119 (H2AK119ub), leading to transcriptional repression of SOCS3. Furthermore, knockdown of SOCS3 rescues the reduced migration and invasion caused by CBX7 depletion in LUAD cells. Together, our findings identify CBX7 as a positive regulator of LUAD metastasis and suggest its potential as a therapeutic target for LUAD treatment.

2025-07-21 | GSE303088 | GEO

Denaturing CLIP (dCLIP) pipeline identifies discrete RNA footprints on chromatin-associated proteins and reveals that CBX7 targets 3’UTRs to regulate mRNA expression

Project description:Interaction networks between chromatin complexes and long noncoding RNAs have become a recurrent theme in epigenetic regulation. However, technical limitations have precluded identification of RNA binding motifs for chromatin-associated proteins. Here we add a denaturation step to UV-crosslink RNA immunoprecipitation (dCLIP), and apply dCLIP to mouse and human chromobox homolog 7 (CBX7), an RNA-binding subunit of Polycomb repressive complex 1 (PRC1). In both species, CBX7 predominantly binds 3’ untranslated regions (UTRs) of messenger RNAs. CBX7 binds with a median RNA “footprint” of 171-183 nucleotides, the small size of which facilitates motif identification by bioinformatics. We find four families of consensus RNA motifs in mouse, and independent analysis of human CBX7 dCLIP data identifies similar motifs. Their mutation abolishes CBX7 binding in vitro. Pharmacological intervention with antisense oligonucleotides paradoxically increases CBX7 binding and enhances gene expression. These data support the utility of dCLIP and reveal an unexpected functional interaction between CBX7 and the 3’UTRs of mRNA.interacts with a range of transcripts, it predominantly binds 3’ untranslated regions (UTRs) of messenger RNAs. CBX7 has a median RNA “footprint” of 171 nucleotides, enabling identification of four families of motifs that tend to co-cluster in the 3’UTR. Manipulating the CBX7-3’UTR interactions and motifs with antisense oligonucleotides results in upregulation of mRNA and protein expression, thereby validating the dCLIP method and revealing functional interactions between CBX7 and mRNA.

2017-10-25 | GSE88823 | GEO

CBX7 is a tumour suppressor that inhibits bladder cancer

Project description:The Polycomb Group Proteins (PcG) are epigenetic regulatory complexes, dysregulation of which has been associated with multiple biological processes, including maintenance of cell identity, differentiation, proliferation, and cancer progression.PcGs form two multiprotein complexes, Polycomb repressive complex 1 (PRC1) and PRC2(1).The PRC2 protein complex mainly consists of Early embryonic deficient (EED), Suppressor of Zeste (SUZ12) and Enhancer of Zeste (EZH), which can catalyzes the trimethylation of histone H3 lysine 27 (H3K27me3), thereby leaving a transcriptionally repressive mark on the chromatin . Such alterations are recognized and read by canonical PRC1 which is composed of CBX (polycomb), PCGF (polycomb group factor), HPH (human polyhomeotic homolog), and the E3-ligase protein (RING) that catalyzes the monoubiquitination of histone H2A on lysine 119 (H2AK119ub1). The H3K27me3 mark is identified by and binds to the chromodomain within the CBX protein in PRC1, thereby ubiquitinating H2AK119 via the RING proteins. The interaction of PRC2 and PRC1 in chromatin contributes to chromatin compaction and transcriptional silencing of target genes.There are five chromobox proteins in humans, CBX2, 4, 6, 7 and 8. Increasing evidence supports essential roles of CBX proteins in tumorigenesis. Remarkably, CBX proteins have shown an opposite function in distinct cancer types in tumor development. For example, CBX7 is overexpressed in ovarian and prostate cancer , implying its oncogenic role in these tumor types. In contrast, CBX7 functions as a tumor suppressor and loss of CBX7 has been associated with increasing the malignancy grade in bladder, breast, pancreatic, glioma, and colon carcinomas (3 4 5 6 7), but its tumor suppression mechanism is unclear.

2021-06-15 | GSE158244 | GEO

Polycomb CBX7 represses expression of tumor suppressor genes

2009-09-23 | GSE10541 | GEO

Gene expression data from UMUC-14 following FGFR3 knock-down using FGFR3 siRNAs

Project description:To better understand the molecular mechanisms underlying altered-FGFR3 oncogenic activity in bladder carcinomas, we made use of UMUC-14 cell lines, which endogenously expressed a mutated activated form of FGFR3 (FGFR3-S249C), the growth and transformation of these cell lines being dependent on activated-FGFR3 activity. We conducted a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not with FGFR3 siRNAs.

2020-12-31 | GSE125547 | GEO

FGFR3 knock-down

Project description:FGFR3 knock-down

| PRJNA330963 | ENA

Polycomb CBX7 represses expression of tumor suppressor genes

Project description:Polycomb CBX7 was stably expressed in embryonal carcinoma cells in order to identify target genes. The study was specifically geared toward unveiling gene targets that are susceptible to DNA hypermethylation in adult cancer. A number of CBX7 target tumor suppressor genes were thereby identified and used in further studies to characterize the mechanism surrounding CBX7 mediated gene suppression. Keywords: CBX7 target gene identification A cDNA encoding the ORF of polycomb CBX7 under the control of EF1alpha promoter was transfected into the Tera-2 embryonal carcinoma cell line. Empty vector was used to transfect control cells. The cells were subject to stable selection using puromycin and a pooled population of CBX7 overexpressing cells was established. Gene expression analysis was performed by comparing the gene expression profile of CBX7 cells to empty vector control cells.

2009-09-23 | E-GEOD-10541 | biostudies-arrayexpress

Gene expression data from MGH-U3 following FGFR3 knock-down using FGFR3 siRNAs

Project description:To better understand the molecular mechanisms underlying altered-FGFR3 oncogenic activity in bladder carcinomas, we made use of MGH-U3 cell lines, which were derived from a human bladder tumor and endogenously expressed a mutated activated form of FGFR3 (FGFR3-Y375C), the growth and transformation of these cell lines being dependent on activated-FGFR3 activity. We conducted a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not with FGFR3 siRNAs.

2018-02-16 | GSE84731 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data