CBX7 is a tumour suppressor that inhibits bladder cancer
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ABSTRACT:
PROVIDER: PRJNA664510 | ENA |
REPOSITORIES: ENA
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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
Project description:TET1 is a tumour suppressor that inhibits bladder cancer progression
| PRJNA566145 | ENA
Project description:Ten-Eleven Translocation 1 (TET1) is a member of methylcytosine dioxygenase, which catalyse 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) that promote the demethylation process. The diminished expression of TET1 protein and 5-hmC in many tumors indicate a critical role for the maintenance of cell stability. However, role of TET1 in bladder cancer development remains unclear. Here we found that TET1 expression was downregulated in bladder cancer tissues compared with normal urothelium and was inversely related to patient overall survival. TET1 silencing in bladder cancer cells increase proliferation and inhibited cell migration and invasion while its re-expression inhibits their proliferation and the growth of tumor xenografts. Furthermore, we found that TET1 binds to the promoter of the TSG to maintain its hypomethylated which interacts with β-catenin and suppress its nuclear translocation, thus inhibiting β-catenin transcriptional activity and downstream genes. In conclusion, TET1 acts as a tumor suppressor gene in bladder cancer cells by suppressing β-catenin signaling. This study may facilitate efforts to therapeutic strategy for patients with bladder cancer.
2020-06-16 | GSE137646 | GEO
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
2009-09-23 | GSE10541 | GEO
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
Project description:Bladder tumours used to construct a tumour stage classifier Keywords = bladder cancer, disease stages, classification Keywords: other
2002-12-08 | GSE89 | GEO
Project description:Purpose: miR-181 is upregulated in human liver cancer. The cancer genome atlas (TCGA) liver cancer data show that the iCluster1 subclass of hepatocellular carcinoma (HCC) has a higher expression of miR-181 than either the iCluster2 or iCluster3 subclass, suggesting it may be a driver of oncogenesis. However, the miR-181 family has also been reported to inhibit tumour progression. Thus, we aim to examine the function of miR-181 and its vital mediators in hepatocarcinogenesis. Methods: Primary liver tumours were induced with diethylnitrosamine (DEN) in global (miR-181ab1GKO), liver-specific (miR-181ab1LKO) and hematopoietic & endothelial lineage-specific (miR-181ab1vavKO) miR-181ab1 deletion mice. The molecular and cellular characterization was carried out using immunohistochemistry and whole-genome transcriptome analysis. Liver-specific miR-181a and CBX7 double knockout mice were used to investigate the role of CBX7 in mediating miR-181 effects on liver tumour progression. An AAV/Transposase Hybrid-Vector System used in this study gave a reliable long-term expression of CBX7 in vivo. Relevant gene expression profiles and patient outcomes were downloaded from TCGA database, and their correlations were analysed. The mRNA profiles of miR-181ab1 wild-type (WT) and knockout (KO) mice were generated by deep sequencing, in triplicate, using Illumina HiSeq. After quality control procedures, short reads were mapped to mouse genome assembly (mm10) by STAR version 2.7.3a. Mapped reads were quantified by featureCounts version 2.0.0 from Subread package. Ward’s hierarchical clustering method was applied to group the samples based on the gene expression matrix. Differential gene expression analysis was then conducted using R package Limma. Gene set enrichment analysis was subsequently performed with R package clusterProfiler. Overlaps between differential expressed gene sets and gene sets in MSigDB were computed with Gene Set Enrichment Analysis (GSEA). Results: The number and size of liver tumours in 181ab1GKO mice were significantly reduced by 50% and 90%, respectively, compared to WT mice at 34-week post-DEN injection. The number of tumours in 181ab1LKO mice was no different from that of control mice, but the size of liver tumours was significantly reduced by 90%. The number and size of tumours were similar in miR-181ab1vavKO and WT mice. Consistent with the roles of miR-181 in the promotion of epithelial to mesenchymal transition (EMT), the TGF-beta signalling pathway was inhibited in 181ab1GKO tumours compared with WT tumours, and expression of E-Cadherin, an EMT marker, was significantly increased in miR-181ab1 KO tumours compared to WT tumours. CBX7 was reduced in WT liver tumours compared to non-tumours, and restored CBX7 expression inhibited the progression of liver tumours in WT mice. At the same time, CBX7 was upregulated in miR-181ab1 KO tumours compared to WT tumours, and CBX7 deletion turned the reduced progression of miR-181ab1 KO liver tumours back to WT liver tumours. MiR-181a expression was the lowest and CBX7 expression the highest in iCluster 2 & 3 subclasses of human HCC compared to iCluster 1. Gene expression profiles were significantly overlapped between human low proliferative periportal-type HCCs and miR-181ab1 KO tumours. Conclusions: Primary liver tumour progression is inhibited by loss of miR-181ab1 via up-regulation of CBX7 expression at the level of the liver cancer cells themselves, but tumour induction requires both hepatic and non-hepatic expression. Tumours in miR-181ab1 KO mice resemble low-proliferative periportal-type human HCC and could represent a new model to study therapies for such difficult-to-treat tumours.
2023-01-31 | GSE196008 | GEO
Project description:High-salt diet inhibits tumour growth in mice via regulating myeloid-derived suppressor cells differentiation
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Project description:Bladder tumours used to construct a tumour stage classifier
2007-09-28 | E-GEOD-89 | biostudies-arrayexpress
Project description:The contribution of the majority of frequently mutated genes to tumourigenesis is not fully defined. Many aggressive human cancers, such as triple negative breast cancers (TNBCs), have a poor prognosis and lack tractable biomarkers and targeted therapeutic options. Here, we systematically characterize loss-of-function mutations to generate a functional map of novel driver genes in a 3-dimensional model of breast cancer heterogeneity that more readily recapitulates the unfavourable tumour microenvironment in vivo. This identified the histone acetyltransferase CREBBP as a potent tumour suppressor gene whose silencing provided a 3D-specific growth advantage only under oxygen and nutrient deplete conditions. CREBBP protein expression was altered in a substantial proportion of TNBCs as well as several other solid tumours, including endometrial, bladder, ovarian and squamous lung cancers. In multiple primary tumours and cell models, loss of CREBBP activity resulted in upregulation of the FOXM1 transcriptional network. Strikingly, treatment with a range of CDK4/6 inhibitors (CDK4/6i), that indirectly target FOXM1 activity, selectively impaired growth in both CREBBP-altered spheroids and cell line xenografts and patient derived models from multiple tumour types. This study is the first to provide rationale for CREBBP as a biomarker for CDK4/6i response in cancer representing a new treatment paradigm for tumours that harbour CREBBP alterations that have limited therapeutic options.
2022-03-23 | PXD012098 | Pride