Global role of IGF2BP1 in controlling the expression of Wnt/ß-catenin-regulated genes [MEF_RNA-seq]
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/ß-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 ß-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. Overall design: To study the difference in DEG's between (MEF-Wnt3a Vs MEF) and (MEF-IGF2BP1-KO-Wnt3a Vs MEF-IGF2BP1-KO)