Similar Datasets
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
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 | GSE237658 | GEO
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 | GSE237688 | GEO
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 | GSE237687 | GEO
Project description:BACKGROUND: Wnt/beta-catenin pathway has critical roles in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of this pathway, little is known regarding Wnt/beta-catenin pathway modification of the cellular apoptosis. METHODS: To identify potential genes regulated by Wnt/beta-catenin pathway and involved in apoptosis, we used a stably integrated, inducible RNA interference (RNAi) vector to specific inhibit the expression and the transcriptional activity of beta-catenin in HeLa cells. Meanwhile, we designed an oligonucleotide microarray covering 1384 apoptosis-related genes. Using oligonucleotide microarrays, a series of differential expression of genes was identified and further confirmed by RT-PCR. RESULTS: Stably integrated inducible RNAi vector could effectively suppress beta-catenin expression and the transcriptional activity of beta-catenin/TCF. Meanwhile, depletion of beta-catenin in this manner made the cells more sensitive to apoptosis. 130 genes involved in some important cell-apoptotic pathways, such as PTEN-PI3K-AKT pathway, NF-kappaB pathway and p53 pathway, showed significant alteration in their expression level after the knockdown of beta-catenin. CONCLUSION: Coupling RNAi knockdown with microarray and RT-PCR analyses proves to be a versatile strategy for identifying genes regulated by Wnt/beta-catenin pathway and for a better understanding the role of this pathway in apoptosis. Some of the identified beta-catenin/TCF directed or indirected target genes may represent excellent targets to limit tumor growth.
| S-EPMC1574340 | biostudies-literature
Project description:BackgroundDeregulation of Wnt/β-catenin signaling is a hallmark of the majority of sporadic forms of colorectal cancer and results in increased stability of the protein β-catenin. β-catenin is then shuttled into the nucleus where it activates the transcription of its target genes, including the proto-oncogenes MYC and CCND1 as well as the genes encoding the basic helix-loop-helix (bHLH) proteins ASCL2 and ITF-2B. To identify genes commonly regulated by β-catenin in colorectal cancer cell lines, we analyzed β-catenin target gene expression in two non-isogenic cell lines, DLD1 and SW480, using DNA microarrays and compared these genes to β-catenin target genes published in the PubMed database and DNA microarray data presented in the Gene Expression Omnibus (GEO) database.ResultsTreatment of DLD1 and SW480 cells with β-catenin siRNA resulted in differential expression of 1501 and 2389 genes, respectively. 335 of these genes were regulated in the same direction in both cell lines. Comparison of these data with published β-catenin target genes for the colon carcinoma cell line LS174T revealed 193 genes that are regulated similarly in all three cell lines. The overlapping gene set includes confirmed β-catenin target genes like AXIN2, MYC, and ASCL2. We also identified 11 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that are regulated similarly in DLD1 and SW480 cells and one pathway - the steroid biosynthesis pathway - was regulated in all three cell lines.ConclusionsBased on the large number of potential β-catenin target genes found to be similarly regulated in DLD1, SW480 and LS174T cells as well as the large overlap with confirmed β-catenin target genes, we conclude that DLD1 and SW480 colon carcinoma cell lines are suitable model systems to study Wnt/β-catenin signaling and associated colorectal carcinogenesis. Furthermore, the confirmed and the newly identified potential β-catenin target genes are useful starting points for further studies.
| S-EPMC3909937 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-04-25 | GSE77365 | GEO
Project description:To validate the suitability of two commonly used colorectal cancer cell lines, DLD1 and SW480, as model systems to study colorectal carcinogenesis, we treated these cell lines with beta-catenin siRNA and identified beta-catenin target genes using DNA microarrays. The list of identified target genes was compared to previously published beta-catenin target genes found in the PubMed and the GEO databases. Based on the large number of beta-catenin target genes found to be similarly regulated in DLD1, SW480 and LS174T as well as the large overlap with confirmed β-catenin target genes, we conclude that DLD1 and SW480 colon carcinoma cell lines are suitable model systems to study beta-catenin regulated genes and signaling pathways 12 arrays (2 cell lines, 2 treatments, 3 biological replicates)
2013-12-31 | E-GEOD-44097 | biostudies-arrayexpress
Project description:Over 400 million years ago, the evolution of vertebrates gave rise to a life cycle in which the organism began to live longer particularly as an adult. To accommodate such a longer lifespan, the organism underwent adaptation, developing a mechanism for long-lived cellular homeostasis. This adaptation required a population of long-lived relatively quiescent somatic stem cells (SSCs) along with a more proliferative differentiated daughter cell population, and was necessary to safeguard the genetic attributes with which SSCs were endowed. Intriguingly, cAMP response element binding protein (CREB)-binding protein (CBP) and E1A-binding protein, 300 kDa (p300), the highly homologous Kat3 coactivators had diverged, through duplication of ancestral Kat3, immediately preceding the evolution of vertebrates, given that both CBP and p300 have been detected in nearly all vertebrates versus non-vertebrates. We now demonstrate that a relatively small, highly evolutionarily conserved, amino terminal 9 amino acid deletion in CBP versus p300, plays a critical role in allowing for both robust maintenance of genomic integrity in stem cells and the initiation of a feed-forward differentiation mechanism by tightly controlling the interaction of the nuclear receptor family with the Wnt signaling cascade in either an antagonistic or synergistic manner.
| S-EPMC6051640 | biostudies-literature
Project description:Ovarian serous carcinoma is a highly aggressive neoplastic disease in women. Our previous studies have demonstrated Notch3 gene amplification and upregulation in many ovarian serous carcinomas and Notch pathway activity contributed to drug resistance. Among different Notch3 ligands, Jagged1 is most dominant in ovarian cancer, and Notch3 pathway activity correlated with Jagged1 expression level in ovarian carcinoma tissues. In this study, we found that Jagged1 expression depended on Notch3 pathway activation. Knockdown of either Notch3 or RBPjk, a Notch-interacting transcription factor critical in Notch signaling, suppressed Jagged1 expression in ovarian cancer cells. Moreover, Jagged1 expression was upregulated in human ovarian surface epithelial cells after ectopic expression of Notch3 intracellular domain and was upregulated in mouse epithelial cells isolated from Notch3-inducible mice after induction. We also found that inhibition of Wnt/β-catenin signaling reduced Jagged1 expression, and co-administration of shRNAs targeting both Notch3 and β-catenin reduced Jagged1 expression much more than targeting either individual gene. Taken together, our data suggested a positive regulatory loop between Notch3 and its ligand, Jagged1, in ovarian cancer cells. In addition, Wnt/β-catenin pathway activation also up-regulated Jagged1. Both mechanisms may sustain Notch3 signaling in ovarian cancer cells and contribute to the pathogenesis of ovarian carcinoma.
| S-EPMC2953807 | biostudies-literature