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The RNA binding protein IGF2BP3 promotes hematopoietic progenitor cell proliferation by targeting leukemogenic pathways

ABSTRACT: The goal of this study was to determine IGF2BP3 RNA targets in human B-cell Acute Lymphocitic Leukemia cell models.

ORGANISM(S): Homo sapiens

PROVIDER: GSE76931 | GEO | 2016/01/16

SECONDARY ACCESSION(S): PRJNA308961

REPOSITORIES: GEO

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The RNA binding protein IGF2BP3 promotes hematopoietic progenitor cell proliferation by targeting leukemogenic pathways

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

2016-01-16 | E-GEOD-76931 | biostudies-arrayexpress

RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation.

Project description: Not available

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The RNA binding protein IGF2BP3 is required MLL-AF4 mediated leukemogenesis

Project description:In our study, we found that MLL-AF4 transcriptionally induces IGF2BP3 and is required for MLL-Af4 mediated leukemogenesis. Deletion of murine Igf2bp3 significantly increased the survival of mice with MLL-Af4 driven leukemia and greatly attenuated disease. Furthermore, Igf2bp3 was necessary for the development of and the self-renewal capacity of MLL-Af4 leukemic initiating cells. eCLIP and transcriptome analysis of MLL-Af4 transformed stem and progenitor cells and primary cells from MLL-Af4 leukemic mice revealed an IGF2BP3-regulated post-transcriptional operon governing tumor cell survival and proliferation. Critical mRNA targets include the Hoxa locus and numerous genes within the Ras signaling pathway. Together, our findings show that IGF2BP3 is an essential positive regulator of MLL-AF4 mediated leukemogenesis and is a potential therapeutic target in this disease.

2021-08-11 | GSE156115 | GEO

IGF2BP3 controls cancer cell invasiveness by modulation RISC function

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

2016-03-12 | E-GEOD-79147 | biostudies-arrayexpress

Metabolic Reprogramming Driven by IGF2BP3 Promotes Acquired Resistance to EGFR Inhibitors in Non–Small Cell Lung Cancer

Project description:Acquired resistance represents a bottleneck for effective molecular targeted therapy in lung cancer. Metabolic adaptation is a distinct hallmark of human lung cancer that might contribute to acquired resistance. In this study, we discovered a novel mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKI) mediated by IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming through the IGF2BP3–COX6B2 axis. IGF2BP3 was upregulated in patients with TKI-resistant non–small cell lung cancer, and high IGF2BP3 expression correlated with reduced overall survival. Upregulated expression of the RNA binding protein IGF2BP3 in lung cancer cells reduced sensitivity to TKI treatment and exacerbated the development of drug resistance via promoting oxidative phosphorylation (OXPHOS). COX6B2 mRNA bound IGF2BP3, and COX6B2 was required for increased OXPHOS and acquired EGFR-TKI resistance mediated by IGF2BP3. Mechanistically, IGF2BP3 bound to the untranslated region of COX6B2 in an m6A-dependent manner to increase COX6B2 mRNA stability. Moreover, the IGF2BP3–COX6B2 axis regulated nicotinamide metabolism, which can alter OXPHOS and promote EGFR-TKI acquired resistance. Inhibition of OXPHOS with IACS-010759, a small-molecule inhibitor, resulted in strong growth suppression in vitro and in vivo in a gefitinib-resistant patient-derived xenograft model. Collectively, these findings suggest that metabolic reprogramming by the IGF2BP3–COX6B2 axis plays a critical role in TKI resistance and confers a targetable metabolic vulnerability to overcome acquired resistance to EGFR-TKIs in lung cancer.

2023-05-09 | GSE231938 | GEO

RIP-sequence of IGF2BP3 in Ishikawa cells

Project description:To explain the possible molecular mechanism underlying the oncogenic roles of IGF2BP3 in EC, we employed RNA immunoprecipitation (RIP) assays to identify the lncRNAs involved in the regulation of IGF2BP3 function. RIP experiments, high-throughput sequencing and data analysis were performed by Seqhealth Tech (Wuhan, China). RIP assays were carried out on Ishikawa cells. The cells were lysed, and the lysis samples for immunoprecipitation reactions were incubated with anti-IGF2BP3 antibody (ab177477, Abcam, USA) or rabbit IgG (Cell Signaling Technology). The library products were enriched, quantified and finally sequenced on the Illumina PE150 platform.One hundred ninety-one candidates as IGF2BP3-interacting lncRNAs were identified in the RIP-seq results.

2022-03-16 | GSE198620 | GEO

Potential Roles of IGF2BP3 in Bladder Cancer [RNA-Seq]

Project description:TCGA data analysis and clinical sample test results showed the IGF2BP3 is highly expressed in bladder cancer and related to tumor metastasis and invasion. RNA sequencing results of clinical bladder tissue from 53 cases showed that the IGF2BP3 expression is related to cell proliferation genes. M6a and RNA sequencing results showed the IGF2BP3 affects the growth, proliferation, and apoptosis of T24 cells, and SpHK1, POMT2, and MRPS18a may be potential targets of IGF2BP3.

2024-03-27 | GSE171022 | GEO

Potential Roles of IGF2BP3 in Bladder Cancer [m6A-seq]

2024-03-27 | GSE171023 | GEO

Effect of IGF2BP3 in the development of glioma

Project description:To investigate the function IGF2BP3 in the regulation of tumor occurrence and development, we established 4 U87MG cell lines in which IGF2BP3 gene has been knocked out and overexpression.

2023-06-29 | GSE235828 | GEO

RNA immunoprecipitation (RIP) of IGF2BP3 from pancreatic cancer cell extracts cultured on fibronectin

Project description:IGF2BP3-bound transcripts were identified by RNA immunoprecipitation and sequencing (RIP-Seq) and bioinformatics analysis. A pancreatic cancer cell line S2-013 was cultured on fibronectin. We performed RIP of IGF2BP3 using anti-IGF2BP3 antibody from the fibronectin-stimulated S2-013 extracts, and identified the associated mRNAs using a next generation sequencer.

2016-11-09 | GSE47597 | GEO

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