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FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer

ABSTRACT: FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer

PROVIDER: PRJNA881309 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21607111.fastq.gz	Fastqsanger.gz
	SRR21607112_1.fastq.gz	Fastqsanger.gz
	SRR21607112_2.fastq.gz	Fastqsanger.gz
	SRR21607113.fastq.gz	Fastqsanger.gz
	SRR21607114_1.fastq.gz	Fastqsanger.gz

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FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer

Project description:Bladder cancer is mostly present in the form of urothelium carcinoma, causing over 150.000 deaths each year. Its histopathological classification as muscle invasive and non-muscle invasive is the most prominent aspect, affecting the prognosis and progression of this disease. In this study, we defined the active regulatory landscape of MIBC and NMIBC cell lines using H3K27ac-seq and used an integrative data approach to combine our findings with existing data. Our analysis revealed FRA1 and FLI1 as the two critical transcription factors differentially regulating MIBC regulatory landscape. Importantly, we show that FRA1 and FLI1 regulate the genes involved in epithelial cell migration and cell junction organization. Knock-down of FRA1 and FLI1 in MIBC revealed the downregulation of several EMT-related genes such as MAP4K4 and FLOT1. Further, ChIP-SICAP performed for FRA1 and FLI1 enabled us to infer chromatin binding partners of these two transcription factors and link this information with their target genes, providing a comprehensive regulatory circuit for the genes implicated in invasive ability of the bladder cancer cells. Finally, we show that knock-down of FRA1 and FLI1 results in statistically significant less migration of cells using IC-CHIP assays. Our results collectively highlight the role of these two transcription factors in invasive characteristics of bladder cancer in selection and design of targeted options for treatment of MIBC.

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FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer

Project description:Identification of transcriptional regulatory networks in muscle invasive and non-muscle invasive bladder cancer cell lines

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FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer.

Project description:Bladder cancer is mostly present in the form of urothelium carcinoma, causing over 150,000 deaths each year. Its histopathological classification as muscle invasive (MIBC) and non-muscle invasive (NMIBC) is the most prominent aspect, affecting the prognosis and progression of this disease. In this study, we defined the active regulatory landscape of MIBC and NMIBC cell lines using H3K27ac ChIP-seq and used an integrative approach to combine our findings with existing data. Our analysis revealed FRA1 and FLI1 as two critical transcription factors differentially regulating MIBC regulatory landscape. We show that FRA1 and FLI1 regulate the genes involved in epithelial cell migration and cell junction organization. Knock-down of FRA1 and FLI1 in MIBC revealed the downregulation of several EMT-related genes such as MAP4K4 and FLOT1. Further, ChIP-SICAP performed for FRA1 and FLI1 enabled us to infer chromatin binding partners of these transcription factors and link this information with their target genes. Finally, we show that knock-down of FRA1 and FLI1 result in significant reduction of invasion capacity of MIBC cells towards muscle microenvironment using IC-CHIP assays. Our results collectively highlight the role of these transcription factors in selection and design of targeted options for treatment of MIBC.

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