Similar Datasets
Project description:IMP1/IGF2BP1 enters extracellular vesicles in colorectal cancer
| PRJNA816905 | ENA
Project description:Colorectal cancer (CRC) is a leading cause of cancer-related death. There is an urgent need for new methods of early CRC detection and monitoring to improve patient outcomes. Extracellular vesicles (EVs) are secreted, lipid-bilayer bound, nanoparticles that carry biological cargo throughout the body and in turn exhibit cancer-related biomarker potential. RNA binding proteins (RBPs) are posttranscriptional regulators of gene expression that may provide a link between host cell gene expression and EV phenotypes. Insulin-like growth factor 2 RNA binding protein 1 (IGF2BP1/IMP1) is an RBP that is highly expressed in CRC with higher levels of expression correlating with poor prognosis. IMP1 binds and potently regulates tumor-associated transcripts that may impact CRC EV phenotypes. Our objective was to test whether IMP1 expression levels impact EV secretion and/or cargo. We used RNA sequencing, in vitro CRC cell lines, ex vivo colonoid models, and xenograft mice to test the hypothesis that IMP1 influences EV secretion and/or cargo in human CRC. Our data demonstrate that IMP1 modulates the RNA expression of transcripts associated with extracellular vesicle pathway regulation, but it has no effect on EV secretion levels in vitro or in vivo. Rather, IMP1 appears to affect EV regulation by directly entering EVs in a transformation-dependent manner. These findings suggest that IMP1 has the ability to shape EV cargo in human CRC, which could serve as a diagnostic/prognostic circulating tumor biomarker.NEW & NOTEWORTHY This work demonstrates that the RNA binding protein IGF2BP1/IMP1 alters the transcript profile of colorectal cancer cell (CRC) mRNAs from extracellular vesicle (EV) pathways. IMP1 does not alter EV production or secretion in vitro or in vivo, but rather enters CRC cells where it may further impact EV cargo. Our work shows that IMP1 has the ability to shape EV cargo in human CRC, which could serve as a diagnostic/prognostic circulating tumor biomarker.
| S-EPMC9678429 | biostudies-literature
Project description:Human neurodevelopment requires differentiating neurons to establish large networks of connections in a highly stereotyped manner. Neuronal differentiation in particular, requires RNA-binding proteins to spatiotemporally regulate thousands of different mRNAs. Yet, how these proteins precisely relate to neuronal development and coordinate the expression of functionally coherent genes in a cell type specific manner is only partially understood. To address this, we sought to understand how the paradigmatic RNA-binding protein IMP1/IGF2BP1, an essential developmental factor, selects and regulates its RNA targets transcriptome-wide during the differentiation of human neurons. We used a combination of systemic and molecular analyses to show that IMP1 directly binds to and regulates the expression of a large set of mRNAs that govern microtubule assembly, an essential process and a key driver of neuronal differentiation. We also show that m6A methylation during the transition from neural precursors to neurons drives both the selection of IMP1 mRNA targets and their translation potential. Our findings establish m6A methylation as a key mechanism coordinating the regulatory action of IMP1 on human neuronal architecture.
2024-06-10 | PXD034341 | Pride
Project description:Metabolomics and metagenomics-combined study to diagnose colorectal cancer using gut-microbiome-secreted extracellular vesicles
2020-01-14 | ST001307 | MetabolomicsWorkbench
Project description:Human neurodevelopment requires differentiating neurons to establish large networks of connections in a highly stereotyped manner. Neuronal differentiation in particular requires RNA-binding proteins to spatiotemporally regulate thousands of different mRNAs. Yet how these proteins precisely relate to neuronal development and coordinate the expression of functionally coherent genes in a cell type specific manner is only partially understood. To address this, we sought to clarify how the paradigmatic RNA-binding protein IMP1/IGF2BP1, an essential developmental factor, selects and regulates its RNA targets transcriptome-wide during the differentiation of human pluripotent stem cell-derived neural precursor cells to their neuronal counterparts. We used a combination of systemic and molecular analyses to show that IMP1 directly binds to and regulates the expression of a large sets of mRNAs.
2024-04-13 | GSE203569 | GEO
Project description:Human neurodevelopment requires differentiating neurons to establish large networks of connections in a highly stereotyped manner. Neuronal differentiation in particular requires RNA-binding proteins to spatiotemporally regulate thousands of different mRNAs. Yet how these proteins precisely relate to neuronal development and coordinate the expression of functionally coherent genes in a cell type specific manner is only partially understood. To address this, we sought to clarify how the paradigmatic RNA-binding protein IMP1/IGF2BP1, an essential developmental factor, selects and regulates its RNA targets transcriptome-wide during the differentiation of human pluripotent stem cell-derived neural precursor cells to their neuronal counterparts. We used a combination of systemic and molecular analyses to show that IMP1 directly binds to and regulates the expression of a large sets of mRNAs.
2024-04-13 | GSE203570 | GEO
Project description:Human neurodevelopment requires differentiating neurons to establish large networks of connections in a highly stereotyped manner. Neuronal differentiation in particular requires RNA-binding proteins to spatiotemporally regulate thousands of different mRNAs. Yet how these proteins precisely relate to neuronal development and coordinate the expression of functionally coherent genes in a cell type specific manner is only partially understood. To address this, we sought to clarify how the paradigmatic RNA-binding protein IMP1/IGF2BP1, an essential developmental factor, selects and regulates its RNA targets transcriptome-wide during the differentiation of human pluripotent stem cell-derived neural precursor cells to their neuronal counterparts. We used a combination of systemic and molecular analyses to show that IMP1 directly binds to and regulates the expression of a large sets of mRNAs.
2024-04-13 | GSE203568 | GEO
Project description:Isolation of IMP1 bound mRNAs. Flag-tagged IMP1 was expressed in HEK293 cells. Flag tagged IMP1 was immunoprecipitated and mRNAs isolated. As controls HEK293 cells that do not express Flag-tagged IMP1 was included.
2006-12-31 | E-MEXP-841 | biostudies-arrayexpress
Project description:ZBP1/IMP1 is a RNA binding protein that post-transcriptionally regulates the expression of a handful mRNAs, implicated in maintaining cell polarity and adhesion. We have previously shown that ZBP1 was able to inhibit proliferation and invasiveness of breast carcinoma cells in vitro. To determine important LncRNA for breast tumor growth and metastasis in response to IMP1 expression, LncRNA expression data were obtained from, and compared between the breast cancer cell line MDA231-IMP1 and MDA231/GFP.
2016-12-09 | GSE91057 | GEO
Project description:Long noncoding RNAs (lncRNAs) have been shown to play important roles in diverse biological process, including embryonic development and cell differentiation. Extensive studies have revealed the function and mechanism of those lncRNAs adjacent to protein-coding genes (PCGs), but there are relatively fewer reports about the lncRNAs within gene desert, particularly in human early germ layer differentiation. Here based on transcriptome analysis during human definitive endoderm (DE) differentiation, we identified a “desert” lncRNA named CTD-2501M5.1, a cytoplasm-located transcript with no protein-coding gene nearby within the 50 kb genomic region, highly expressed in human definitive endoderm. Depletion of CTD-2501M5.1 by either shRNA or promoter deletion could cause the deficiency of DE differentiation from human pluripotent stem cells (PSCs). The biochemical analysis showed that CTD-2501M5.1 functionally interacted with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1, also named IMP1), which is necessary for endoderm differentiation demonstrated by loss-of-function assay. We further found depletion of CTD-2501M5.1 could result in reduced WNT signaling activities. More importantly, manipulating WNT activity by chemicals could rescue the phenotype of DE deficiency due to the depletion of CTD-2501M5.1 or IMP1. Mechanistically, CTD-2501M5.1 facilitated the interaction between IMP1 and FZD5 mRNA, stabilizing FZD5 which is required for WNT signaling activation and DE differentiation. Ultimately, our study not only revealed the biological function of a novel desert lncRNA CTD-2501M5.1 in human DE differentiation, but also underlined lncRNA-mediated mRNA stability regulation via IMP1.
2023-03-30 | GSE188501 | GEO