Project description:The goal of this study was to determine IGF2BP3 regulation of RNA targets in human pacreatic ductal adenocarcinoma cell lines Included are iCLIP-seq libraries for IGF2BP3 from PL45 and Panc1 PDAC cell samples, RIP-seq samples from PL45 and Panc1 PDAC cells, RNA-seq data sets from control and IGF2BP3 knockdown in PL45 and Panc1 PDAC cells, and small RNA-seq samples from Panc1 cells
Project description:Transcriptional profiles of two PDAC cell lines (CF_PAC1 and PANC1) are highly divergent. Knocking down IGF2BP3 resulted in significant transcriptional divergence at 24H, 48H and 72H compared to control, most strikingly in the PANC1 cell line. The dominant affect of knockdown was widespread reduction in expression levels of genes functionally enriched for Proliferation, TNFA signalling and Apoptosis. This highlights IGF2BP3 in these cell lines to be acting as a positve regulator of gene programs broadly associated with progression through the cell cycle and identifies many candidate IGF2BP3-linked genes. A high confidence, consistent motif of genes identified as IGF2BP3-regulated in both cell lines included the genes SLC22A18, GET3 and CCNG1.
Project description:We performed RNA sequencing of gene expression of differentiated primary human bronchial epithelial cells derived from control and asthmatic patients, stimulated with IL-13. The Type 2 Asthma mediator IL-13 was described to induce airway hyperresponsiveness, goblet cell metaplasia, mucus hypersecretion and airway remoddeling including impairment of epithelial barrier integrity. We investigated differential expression of SARS-CoV-2 related host gene expression as well as genes involved in N-linked glycosylation upon IL-13 in bronchial epithelial cells. Top IL-13 affected pathways included ion- and transmembrane transport, lipid metabolic processed and protein glycosylation.
Project description:To analyse gene expression differences between differentiated bronchial epithelial cells kept under control conditions or treated for 72 hours with IL-4 (10 ng/ml)
Project description:Ovarian cancer (OC) is the most lethal disease among female reproductive system tumors, particularly epithelial ovarian cancer (EOC). N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNA and is involved in gene expression regulation. In OC, high expression of the m6A reader protein IGF2BP3 predicts a poor prognosis, but the target molecules and mechanisms underlying this association remain unclear. This study demonstrates that IGF2BP3 promotes EOC progression by recognizing and stabilizing m6A-modified FASN mRNA, thereby activating the WNT/β-catenin signaling pathway. This activation enhances lipid synthesis, increases mitochondrial membrane potential, shortens S-phase duration, and promotes cell proliferation and metastasis. Mechanistically, IGF2BP3 binds to m6A-modified FASN mRNA to enhance its stability, and pharmacological inhibition of FASN by orlistat reverses IGF2BP3-mediated oncogenic effects and WNT/β-catenin activation. In vivo and in vitro experiments confirm that knocking down either IGF2BP3 or FASN reverses these malignant phenotypes. These findings highlight a novel m6A-dependent IGF2BP3–FASN–WNT axis that drives EOC progression, providing a potential biomarker for targeted therapy.
Project description:The goal of this study was to determine IGF2BP3 RNA targets in human B-cell Acute Lymphocitic Leukemia cell models. Included are iCLIP-seq libraries for IGF2BP3 from RS4;11 and REH B-ALL cell samples and RNA-seq data sets from control and IGF2BP3 knockdown RS4;11 B-ALL cell lines
Project description:Goblet cell hyperplasia (GCH) is a feature of respiratory diseases characterized by mucus hypersecretion. GCH is driven by Th2 cytokines such as IL-4. To investigate the gene expression changes associated with GCH, we treated human bronchial epithelial cells with IL-4. By microarray analysis and functional studies, we found that IL-4 promotes a profound change that results in enhanced bicarbonate secretion. This change may be required to support mucus release.