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Series GSE195768 Query DataSets for GSE195768
Status Public on May 23, 2024
Title RNA-seq Series of Bladder Carcinoma Tumors
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Background: Muscle-invasive bladder cancer is a common aggressive disease with unmet clinical needs. Recent work established a set of consensus bladder cancer transcriptomic subtypes that distinguishes the cell identity of bladder cancers for improved diagnosis and treatment. However, how these distinct subtypes are regulated remains unclear. Given the link between super-enhancers and the regulation of cell identity, we hypothesized that epigenetic activation of distinct super-enhancers could drive the transcriptional programs of the various bladder cancer subtypes.
Results: Through integrated RNA sequencing and epigenomic profiling of histone marks (H3K27ac, H3K27me3, H3K9me3) in a diverse panel of 15 primary bladder tumours, seven bladder cancer cell lines, and two primary cultures from normal human urothelia, we established the first integrated epigenetic map of bladder cancer and demonstrate the link between bladder cancer subtype and epigenetic control. Through H3K27ac analysis, we identify the repertoire of activated super-enhancers in bladder cancer that distinguish molecular subtypes. Building on these findings, we reveal the super-enhancer-regulated networks of candidate master transcription factors for Luminal and Basal bladder cancer subgroups. We find that FOXA1, a key pioneer factor in Luminal bladder cancers identified in our Luminal transcription factor network, binds subgroup-specific bladder super-enhancers and correlates with their activation. Furthermore, CRISPR-Cas9 inactivating mutation of FOXA1 triggers a shift from Luminal to Basal cell identity. This shift is accompanied by an overexpression of ZBED2, one of the newly identified transcriptional regulators in the Basal-specific transcription factor network. 5Finally, we show that both FOXA1 and ZBED2 play concordant roles in preventing inflammatory response in bladder cancer cells through STAT2 inhibition and promote cancer cell survival.
Conclusions: Overall, our study provides new data for understanding epigenetic regulation of muscle- invasive bladder cancer and identifies a coregulated network of super-enhancers and associated transcription factors as new potential targets for the treatment of this aggressive disease
 
Overall design RNA-seq Series of Bladder carcinoma tumors
 
Contributor(s) Neyret-Kahn H, Radvanyi F, Bernard-Pierrot I, Chapeaublanc E, Fontugne J
Citation(s) 36944729
Submission date Jan 31, 2022
Last update date May 23, 2024
Contact name Elodie chapeaublanc
E-mail(s) elodie.chapeaublanc@pasteur.fr
Organization name Institut Curie
Department UMR 144
Lab Equipe Radvanyi
Street address 26 rue d'ulm
City paris
ZIP/Postal code 75248
Country France
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (15)
GSM5849884 RNA-seq data for sample tumor T2542
GSM5849885 RNA-seq data for sample tumor T839
GSM5849886 RNA-seq data for sample tumor T877
Relations
BioProject PRJNA802123

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE195768_adapter_list_tumors_RNA-seq.csv.gz 169 b (ftp)(http) CSV
GSE195768_matrix_deseq2_tumor.csv.gz 3.0 Mb (ftp)(http) CSV
GSE195768_pipeline_config.txt.gz 260 b (ftp)(http) TXT
GSE195768_tablecounts_raw.csv.gz 1.2 Mb (ftp)(http) CSV
GSE195768_tablecounts_tpm.csv.gz 1.5 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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