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Identification of differentially expressed long non-coding RNAs in bladder cancer

ABSTRACT: As various data suggest that lncRNAs are important in human cancer, we hypothesized that they play a role in urothelial carcinogenesis. To test this hypothesis we analysed 83 normal and malignant urothelial samples using NCode™ Human Non-coding RNA Microarrays for differentially expressed lncRNAs with potential regulatory functions in urothelial cell cancer (UCC). We identified global changes in lncRNA expression that reflect the disease phenotype. We then performed explorative analysis (siRNA gene knock-down and loss-of-function studies) of selected species and identified those with potential prognostic roles. Quantitative real-time PCR was used to validate the microarray findings.

ORGANISM(S): Homo sapiens

PROVIDER: GSE55433 | GEO | 2014/02/28

SECONDARY ACCESSION(S): PRJNA239575

REPOSITORIES: GEO

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Identification of differentially expressed long non-coding RNAs in bladder cancer

Project description:As various data suggest that lncRNAs are important in human cancer, we hypothesized that they play a role in urothelial carcinogenesis. To test this hypothesis we analysed 83 normal and malignant urothelial samples using NCodeM-bM-^DM-" Human Non-coding RNA Microarrays for differentially expressed lncRNAs with potential regulatory functions in urothelial cell cancer (UCC). We identified global changes in lncRNA expression that reflect the disease phenotype. We then performed explorative analysis (siRNA gene knock-down and loss-of-function studies) of selected species and identified those with potential prognostic roles. Quantitative real-time PCR was used to validate the microarray findings. Total RNA was extracted from urothelial samples from 57 patients with UCC (23 low-grade NMI, 14 high-grade NMI and 20 invasive tumours) and from 26 disease free controls.

2014-02-28 | E-GEOD-55433 | biostudies-arrayexpress

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Project description:Urothelial cell carcinoma of the bladder (UCC) is a common disease characterized by FGFR3 mutation. Whilst upregulation of this oncogene occurs most frequently in low-grade non-invasive tumors, recent data reveal increased FGFR3 expression characterizes a common sub-type of invasive UCC sharing genetic similarities with lobular breast cancer. These similarities include upregulation of the FOXA1 transcription factor and reduced expression of microRNAs-99a/100. We have previously identified direct regulation of FGFR3 by these two microRNAs and now search for further targets. Using a microarray meta-database we find potential FOXA1 regulation by microRNAs-99a/100. We confirm direct targeting of the FOXA1 3âUTR by microRNAs-99a/100 and also potential indirect regulation through microRNA-485-5p/SOX5/JUN-D/FOXL1 and microRNA-486/FOXO1a. In 292 benign and malignant urothelial samples, we find an inverse correlation between the expression of FOXA1 and microRNAs-99a/100 (r=-0.33 to -0.43, p<0.05). As for FGFR3 in UCC, tumors with high FOXA1 expression have lower rates of progression than those with low expression (Log rank p=0.009). Using global gene expression and CpG methylation profiling we find genotypic consequences of FOXA1 upregulation in UCC. These are associated with regional hypomethylation and near FOXA1 binding sites, and mirror patterns previously reported in FGFR3 mutant UCC. These include gene silencing through aberrant hypermethylation (e.g. IGFBP3) and affect genes that characterize lobular breast cancer (e.g. ERBB2, XBP1). In conclusion, we have identified microRNAs-99a/100 mediate a direct relationship between FGFR3 and FOXA1, and potentially facilitate cross talk between these pathways in UCC. Gene expression profiling of EJ Bladder cancer cells transfected with FOXA1 construct or with empty pUC19 vector.

2014-08-01 | E-GEOD-56037 | biostudies-arrayexpress

Effect of increased FOXA1 on gene expression in bladder cancer cells

Project description:Urothelial cell carcinoma of the bladder (UCC) is a common disease characterized by FGFR3 mutation. Whilst upregulation of this oncogene occurs most frequently in low-grade non-invasive tumors, recent data reveal increased FGFR3 expression characterizes a common sub-type of invasive UCC sharing genetic similarities with lobular breast cancer. These similarities include upregulation of the FOXA1 transcription factor and reduced expression of microRNAs-99a/100. We have previously identified direct regulation of FGFR3 by these two microRNAs and now search for further targets. Using a microarray meta-database we find potential FOXA1 regulation by microRNAs-99a/100. We confirm direct targeting of the FOXA1 3’UTR by microRNAs-99a/100 and also potential indirect regulation through microRNA-485-5p/SOX5/JUN-D/FOXL1 and microRNA-486/FOXO1a. In 292 benign and malignant urothelial samples, we find an inverse correlation between the expression of FOXA1 and microRNAs-99a/100 (r=-0.33 to -0.43, p<0.05). As for FGFR3 in UCC, tumors with high FOXA1 expression have lower rates of progression than those with low expression (Log rank p=0.009). Using global gene expression and CpG methylation profiling we find genotypic consequences of FOXA1 upregulation in UCC. These are associated with regional hypomethylation and near FOXA1 binding sites, and mirror patterns previously reported in FGFR3 mutant UCC. These include gene silencing through aberrant hypermethylation (e.g. IGFBP3) and affect genes that characterize lobular breast cancer (e.g. ERBB2, XBP1). In conclusion, we have identified microRNAs-99a/100 mediate a direct relationship between FGFR3 and FOXA1, and potentially facilitate cross talk between these pathways in UCC.

2014-08-01 | GSE56037 | GEO

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2014-10-17 | GSE55908 | GEO

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Project description:To gain a more depth knowledge of repressive epigenetic gene regulation in UCC, we have profiled H3K9m3 and H3K27m3 in normal and malignant urothelial cells. We matched these profiles to those 5-methylcytosine and gene expression. We hypothesized that differences represent pro-carcinogenic events within the urothelium. We identified a panel of genes with cancer specific epigenetic mediated aberrant expression. Two repressive histone modifications (H3K9m3 and H3K27m3) , cytosine methylation and gene expression were compared between normal human urothelial cell line (NHU) and malignant urothelial cells (EJ and RT112).

2011-09-19 | E-GEOD-31864 | biostudies-arrayexpress

Epigenetic priming to enhance CAR-T cell cytotoxicity in bladder cancer

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Epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells

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RNA sequencing data for 30 bladder cancer cell lines

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2017-09-14 | GSE97768 | GEO

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