IGF2BP1, a conserved regulator of RNA turnover in cancer [total RNA]
Ontology highlight
ABSTRACT: The IGF2 mRNA binding protein 1 (IGF2BP1) promotes tumor progression in a multitude of solid tumors and its expression is associated with adverse prognosis. The main role proposed for IGF2BP1 in cancer cells is the stabilization of mRNAs encoding pro-oncogenic factors. Several binding studies, however, revealed a plethora of putative IGF2BP1-RNA targets. Thus, at present the main, conserved target RNAs and pathways controlled by IGF2BP1 in cancer remain elusive. In this study, we present a set of genes showing a conserved pattern of deregulation in dependence of IGF2BP1 expression in cancer-derived cell lines. By incorporating publicly available data sets, we further compiled a set of RNAs probably stabilized by IGF2BP1 in cancer and characterized them. Functional enrichment analyses revealed conserved pathways influenced by IGF2BP1 in cancer.
Project description:The IGF2 mRNA binding protein 1 (IGF2BP1) promotes tumor progression in a multitude of solid tumors and its expression is associated with adverse prognosis. The main role proposed for IGF2BP1 in cancer cells is the stabilization of mRNAs encoding pro-oncogenic factors. Several binding studies, however, revealed a plethora of putative IGF2BP1-RNA targets. Thus, at present the main, conserved target RNAs and pathways controlled by IGF2BP1 in cancer remain elusive. In this study, we present a set of genes showing a conserved pattern of deregulation in dependence of IGF2BP1 expression in cancer-derived cell lines. By incorporating publicly available data sets, we further compiled a set of RNAs probably stabilized by IGF2BP1 in cancer and characterized them. Functional enrichment analyses revealed conserved pathways influenced by IGF2BP1 in cancer.
Project description:The IGF2 mRNA binding protein 1 (IGF2BP1) promotes tumor progression in a multitude of solid tumors and its expression is associated with adverse prognosis. The main role proposed for IGF2BP1 in cancer cells is the stabilization of mRNAs encoding pro-oncogenic factors. Several binding studies, however, revealed a plethora of putative IGF2BP1-RNA targets. Thus, at present the main, conserved target RNAs and pathways controlled by IGF2BP1 in cancer remain elusive. In this study, we present a set of genes showing a conserved pattern of deregulation in dependence of IGF2BP1 expression in cancer-derived cell lines. By incorporating publicly available data sets, we further compiled a set of RNAs probably stabilized by IGF2BP1 in cancer and characterized them. Functional enrichment analyses revealed conserved pathways influenced by IGF2BP1 in cancer.
Project description:The IGF2 mRNA-binding protein 1 (IGF2BP1) is a post-transcriptional enhancer of tumor growth. However, conserved effector pathway(s) and the feasibility of targeting IGF2BP1 in cancer cells remained elusive. We demonstrate that IGF2BP1 is a conserved regulator of E2F-driven gene expression and cancer cell cycle progression. IGF2BP1 promotes positive regulators of G1/S transition by stabilizing the respective mRNAs. This regulation is 3’UTR-, miRNA- and m6A-dependent, suggesting a conserved role of m6A-enhanced cell cycle progression across cancers. IGF2BP1 stabilizes E2F-encoding mRNAs and some of their target transcripts revealing a post-transcriptional super-enhancer role of the protein in E2F-driven gene expression. The small molecule BTYNB disrupts this super-enhancer function by impairing IGF2BP1-RNA association and consequently interferes with tumor cell proliferation and tumor growth.
Project description:The IGF2 mRNA-binding protein 1 (IGF2BP1) is a post-transcriptional enhancer of tumor growth. However, conserved effector pathway(s) and the feasibility of targeting IGF2BP1 in cancer cells remained elusive. We demonstrate that IGF2BP1 is a conserved regulator of E2F-driven gene expression and cancer cell cycle progression. IGF2BP1 promotes positive regulators of G1/S transition by stabilizing the respective mRNAs. This regulation is 3’UTR-, miRNA- and m6A-dependent, suggesting a conserved role of m6A-enhanced cell cycle progression across cancers. IGF2BP1 stabilizes E2F-encoding mRNAs and some of their target transcripts revealing a post-transcriptional super-enhancer role of the protein in E2F-driven gene expression. The small molecule BTYNB disrupts this super-enhancer function by impairing IGF2BP1-RNA association and consequently interferes with tumor cell proliferation and tumor growth.
Project description:The IGF2 mRNA-binding protein 1 (IGF2BP1) is a post-transcriptional enhancer of tumor growth. However, conserved effector pathway(s) and the feasibility of targeting IGF2BP1 in cancer cells remained elusive. We demonstrate that IGF2BP1 is a conserved regulator of E2F-driven gene expression and cancer cell cycle progression. IGF2BP1 promotes positive regulators of G1/S transition by stabilizing the respective mRNAs. This regulation is 3’UTR-, miRNA- and m6A-dependent, suggesting a conserved role of m6A-enhanced cell cycle progression across cancers. IGF2BP1 stabilizes E2F-encoding mRNAs and some of their target transcripts revealing a post-transcriptional super-enhancer role of the protein in E2F-driven gene expression. The small molecule BTYNB disrupts this super-enhancer function by impairing IGF2BP1-RNA association and consequently interferes with tumor cell proliferation and tumor growth.
Project description:The IGF2 mRNA-binding protein 1 (IGF2BP1) is a post-transcriptional enhancer of tumor growth. However, conserved effector pathway(s) and the feasibility of targeting IGF2BP1 in cancer cells remained elusive. We demonstrate that IGF2BP1 is a conserved regulator of E2F-driven gene expression and cancer cell cycle progression. IGF2BP1 promotes positive regulators of G1/S transition by stabilizing the respective mRNAs. This regulation is 3’UTR-, miRNA- and m6A-dependent, suggesting a conserved role of m6A-enhanced cell cycle progression across cancers. IGF2BP1 stabilizes E2F-encoding mRNAs and some of their target transcripts revealing a post-transcriptional super-enhancer role of the protein in E2F-driven gene expression. The small molecule BTYNB disrupts this super-enhancer function by impairing IGF2BP1-RNA association and consequently interferes with tumor cell proliferation and tumor growth.
Project description:The IGF2 mRNA-binding protein 1 (IGF2BP1) is a post-transcriptional enhancer of tumor growth. However, conserved effector pathway(s) and the feasibility of targeting IGF2BP1 in cancer cells remained elusive. We demonstrate that IGF2BP1 is a conserved regulator of E2F-driven gene expression and cancer cell cycle progression. IGF2BP1 promotes positive regulators of G1/S transition by stabilizing the respective mRNAs. This regulation is 3’UTR-, miRNA- and m6A-dependent, suggesting a conserved role of m6A-enhanced cell cycle progression across cancers. IGF2BP1 stabilizes E2F-encoding mRNAs and some of their target transcripts revealing a post-transcriptional super-enhancer role of the protein in E2F-driven gene expression. The small molecule BTYNB disrupts this super-enhancer function by impairing IGF2BP1-RNA association and consequently interferes with tumor cell proliferation and tumor growth.
Project description:The IGF2 mRNA-binding protein 1 (IGF2BP1) is a post-transcriptional enhancer of tumor growth. However, conserved effector pathway(s) and the feasibility of targeting IGF2BP1 in cancer cells remained elusive. We demonstrate that IGF2BP1 is a conserved regulator of E2F-driven gene expression and cancer cell cycle progression. IGF2BP1 promotes positive regulators of G1/S transition by stabilizing the respective mRNAs. This regulation is 3’UTR-, miRNA- and m6A-dependent, suggesting a conserved role of m6A-enhanced cell cycle progression across cancers. IGF2BP1 stabilizes E2F-encoding mRNAs and some of their target transcripts revealing a post-transcriptional super-enhancer role of the protein in E2F-driven gene expression. The small molecule BTYNB disrupts this super-enhancer function by impairing IGF2BP1-RNA association and consequently interferes with tumor cell proliferation and tumor growth.
Project description:The oncofetal IGF2 mRNA binding protein (IGF2BP) family modulates tumor cell properties but IGF2BP paralogue-specific roles remain poorly understood. We demonstrate that phenotypic roles of IGF2BPs vary in a cancer cell-dependent manner. However, only IGF2BP1 shows oncogenic potential in all cancer cells analyzed. Consistently, only IGF2BP1 expression is associated with poor prognosis in ovarian carcinoma and promotes all oncogenic properties analyzed in ovarian cancer-derived tumor cells. Despite a substantial overlap of candidate target mRNAs of IGF2BP paralogues proposed by CLIP analyses, the paralogue-specific depletion of IGF2BPs induces strikingly distinct deregulation of mRNA abundance. Transcripts decreased by IGF2BP1 depletion or knockout are enriched for IGF2BP1- as well as AGO-CLIP hits conserved in distinct cell lines, are prone to targeting by highly abundant miRNAs and comprise significantly longer 3’UTRs. Downregulation of target mRNAs upon IGF2BP1 depletion is abrogated when miRNAs are expressed at low levels or depleted by DICER/DROSHA knockdown. Strikingly, the depletion of all 12 randomly selected miRNA-prone target mRNAs impairs at least one analyzed IGF2BP1-modulated tumor cell property. These findings indicate that IGF2BPs serve distinct roles in cancer-derived cells and suggest that IGF2BP1’s main role is the post-transcriptional, miRNome-dependent enhancement of factors promoting oncogenic tumor cell properties.
Project description:The IGF2 mRNA-binding protein 1 (IGF2BP1) is a post-transcriptional enhancer of tumor growth. However, conserved effector pathway(s) and the feasibility of targeting IGF2BP1 in cancer cells remained elusive. We demonstrate that IGF2BP1 is a conserved regulator of E2F-driven gene expression and cancer cell cycle progression. IGF2BP1 promotes positive regulators of G1/S transition by stabilizing the respective mRNAs. This regulation is 3’UTR-, miRNA- and m6A-dependent, suggesting a conserved role of m6A-enhanced cell cycle progression across cancers. IGF2BP1 stabilizes E2F-encoding mRNAs and some of their target transcripts revealing a post-transcriptional super-enhancer role of the protein in E2F-driven gene expression. The small molecule BTYNB disrupts this super-enhancer function by impairing IGF2BP1-RNA association and consequently interferes with tumor cell proliferation and tumor growth.