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Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes II

ABSTRACT: Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes II

PROVIDER: PRJNA996124 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25322227.fastq.gz	Fastqsanger.gz
	SRR25322228.fastq.gz	Fastqsanger.gz
	SRR25322229.fastq.gz	Fastqsanger.gz
	SRR25322230.fastq.gz	Fastqsanger.gz
	SRR25322231.fastq.gz	Fastqsanger.gz

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Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes II

Project description:The purpose of this study was to determine how IGF2BP1 affects non-transformed and colorectal cancer (CRC) cells' expression of the genes regulated by Wnt/β-catenin signaling. The study established that while the majority of upregulated genes in non-transformed cells were activated by Wnt ligand treatment independent of IGF2BP1, a subset of Wnt-induced genes was regulated by IGF2BP1, including 11 direct binding targets. In contrast, in CRC cells where Wnt signaling is constitutively active, the majority of downregulated genes upon β-catenin/Tcf7l2 blockage were regulated by IGF2BP1, and 17 of these genes were identified as direct binding targets of IGF2BP1. Our iCLIP study identified a shift in the binding regions along target transcriptomes with modulations in Wnt signaling. Furthermore, the study found a significant change in the enrichment of 6-mer motifs associated with IGF2BP1 binding in response to Wnt signaling in both cell types, suggesting a role for Wnt signaling in regulating IGF2BP1 binding specificity. The study also revealed a signature of IGF2BP1-regulated genes that are significantly associated with colon cancer-free survival in humans, as well as potential targets for colon cancer treatment, including MGAT5 and MET. Overall, this study highlights the complex and context-dependent regulation of Wnt signaling target genes by IGF2BP1 in non-transformed and CRC cells and identifies potential targets for colon cancer treatment.

2023-09-19 | GSE237664 | GEO

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes I

2023-09-19 | GSE237658 | GEO

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes [MEF_RNA-seq]

2023-09-19 | GSE237688 | GEO

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes [G109_DLD1_RNA-seq]

2023-09-19 | GSE237687 | GEO

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes

Project description:Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes

| PRJNA996118 | ENA

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes I

Project description:Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes I

| PRJNA996122 | ENA

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes [G109_DLD1_RNA-seq]

Project description:Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes [G109_DLD1_RNA-seq]

| PRJNA996162 | ENA

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes [MEF_RNA-seq]

Project description:Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes [MEF_RNA-seq]

| PRJNA996163 | ENA

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes in colorectal cancer cells.

Project description:Introduction: Wnt/β-catenin signaling controls cell division and lineage specification during embryonic development, and is crucial for stem cells maintenance and gut tissue regeneration in adults. Aberrant activation of Wnt/β-catenin signaling is also essential for the pathogenesis of a variety of malignancies. The RNA-binding protein IGF2BP1 is a transcriptional target of Wnt/β-catenin signaling, normally expressed during development and often reactivated in cancer cells, where it regulates the stability of oncogenic mRNA. Methods: In this study, we employed iCLIP and RNA sequencing techniques to investigate the role of IGF2BP1 in the post-transcriptional regulation of Wnt/β-catenin-induced genes at a global level within colorectal cancer (CRC) cells characterized by constitutively active Wnt/β-catenin signaling. Results and Discussion: In our study, we show that, in contrast to normal cells, CRC cells exhibit a much stronger dependency on IGF2BP1 expression for Wnt/β-catenin-regulated genes. We show that both untransformed and CRC cells have their unique subsets of Wnt/β-catenin-regulated genes that IGF2BP1 directly controls through binding to their mRNA. Our iCLIP analysis revealed a significant change in the IGF2BP1-binding sites throughout the target transcriptomes and a significant change in the enrichment of 6-mer motifs associated with IGF2BP1 binding in response to Wnt/β-catenin signaling. Our study also revealed a signature of IGF2BP1-regulated genes that are significantly associated with colon cancer-free survival in humans, as well as potential targets for CRC treatment. Overall, this study highlights the complex and context-dependent regulation of Wnt/β-catenin signaling target genes by IGF2BP1 in non-transformed and CRC cells and identifies potential targets for colon cancer treatment.

| S-EPMC10565211 | biostudies-literature

Global role of IGF2BP1 in controlling the expression of Wnt/β-catenin-regulated genes

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-19 | GSE237666 | GEO