Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393961 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:U87 cells were transduced with IDH1 WT or IDH1 R132H and stable clones were selected.
2018-07-12 | GSE101291 | GEO
Project description:B7H3 (also known as CD276) is a co-stimulator checkpoint protein of the cell surface B7 superfamily. Recently, the function beyond immune regulation of B7H3 has been widely studied. However, the expression preference and the regulation mechanism underlying B7H3 in different subtypes of gliomas is rarely understood. We show here that B7H3 expression is significantly decreased in IDH-mutated gliomas and in cultured IDH1-R132H glioma cells. Accumulation of 2-HG leads to a remarkable downregulation of B7H3 protein and the activity of IDH1-R132H mutant is responsible for B7H3 reduction in glioma cells. Inhibition of autophagy by inhibitors like leupeptin, chloroquine (CQ), and Bafilomycin A1 (Baf-A1) blocks the degradation of B7H3 in glioma cells. In the meantime, the autophagy flux is more active with higher LC3B-II and lower p62 in IDH1-R132H glioma cells than in IDH1-WT cells. Furthermore, sequence alignment analysis reveals potential LC3-interacting region (LIR) motifs 'F-V-S/N-I/V' in B7H3. Moreover, B7H3 interacts with p62 and CQ treatment significantly enhances this interaction. Additionally, we find that <i>B7H3</i> is positively correlated with <i>VEGFA</i> and <i>MMP2</i> by bioinformatics analysis in gliomas. B7H3 and VEGFA are decreased in IDH-mutated gliomas and further reduced in 2-HG<sup>high</sup> gliomas compared to 2-HG<sup>low</sup> glioma sections by IHC staining. Our study demonstrates that B7H3 is preferentially overexpressed in IDH wild-type gliomas and could serve as a potential theranostic target for the precise treatment of glioma patients with wild-type IDH.
2021-05-26 | MTBLS2692 | MetaboLights
Project description:The cytosolic NADP+-dependent isocitrate dehydrogenase IDH1 is frequently mutated in human cancers. Recent studies have shown that IDH1 mutant primary glioblastomas (GBM) and acute myeloid leukemias (AML) display robust association with CpG island methylator phenotype (CIMP). Such observations bring into question whether IDH1 mutations directly contribute to the development of CIMP or if the hypermethylation phenotype precedes acquisition of IDH1 mutations. To reveal the effects of IDH1 mutations on DNA methylation and gene expression, we introduced the most frequently observed IDH1 mutation, R132H, into a human cancer cell line through gene targeting. We profiled changes in methylation at over 27,000 CpG dinucleotides spanning 14,475 unique gene regions and characterized genome-wide gene expression alterations resulting from IDH1R132H knockin. We observed consistent changes in both DNA methylation and gene expression when comparing two independent IDH1R132H knockin clones to their wild-type parent, and report hypermethylation of over 2,000 loci, the majority of which contained preexisting methylation in IDH1WT parental cells. These loci exhibit the same trend in primary TCGA glioblastoma tumors with mutant IDH1 as compared to those with wild-type IDH1 and have significant overlap with genes hypermethylated in glioma-CIMP+ tumors. Furthermore, we identify specific DNA methylation and gene expression alterations which correlate with IDH1 mutations in our cell-line model as well as primary glioblastomas, including hypermethylation and transcriptional silencing of RBP1. The presented data provide insight on epigenetic alterations induced by IDH1 mutations and support a contributory role for IDH1 mutants in regulation of DNA methylation and gene expression in human cancer cells. Comparison of IDH1 R132H and wild-type HCT116 cells as well as HOG cells overexpressing either wild-type IDH1 or IDH1 R132H
2012-08-13 | E-GEOD-31133 | biostudies-arrayexpress
Project description:Expression profiles in wild-type and IDH1 R132H/WT human astroglial cells [RNA-seq]
| PRJNA401722 | ENA
Project description:DNA methylation profiles in wild-type and IDH1 R132H/WT human astroglial cells [methylation]
| PRJNA401868 | ENA
Project description:The cytosolic NADP+-dependent isocitrate dehydrogenase IDH1 is frequently mutated in human cancers. Recent studies have shown that IDH1 mutant primary glioblastomas (GBM) and acute myeloid leukemias (AML) display robust association with CpG island methylator phenotype (CIMP). Such observations bring into question whether IDH1 mutations directly contribute to the development of CIMP or if the hypermethylation phenotype precedes acquisition of IDH1 mutations. To reveal the effects of IDH1 mutations on DNA methylation and gene expression, we introduced the most frequently observed IDH1 mutation, R132H, into a human cancer cell line through gene targeting. We profiled changes in methylation at over 27,000 CpG dinucleotides spanning 14,475 unique gene regions and characterized genome-wide gene expression alterations resulting from IDH1R132H knockin. We observed consistent changes in both DNA methylation and gene expression when comparing two independent IDH1R132H knockin clones to their wild-type parent, and report hypermethylation of over 2,000 loci, the majority of which contained preexisting methylation in IDH1WT parental cells. These loci exhibit the same trend in primary TCGA glioblastoma tumors with mutant IDH1 as compared to those with wild-type IDH1 and have significant overlap with genes hypermethylated in glioma-CIMP+ tumors. Furthermore, we identify specific DNA methylation and gene expression alterations which correlate with IDH1 mutations in our cell-line model as well as primary glioblastomas, including hypermethylation and transcriptional silencing of RBP1. The presented data provide insight on epigenetic alterations induced by IDH1 mutations and support a contributory role for IDH1 mutants in regulation of DNA methylation and gene expression in human cancer cells. Comparison of IDH1 R132H and wild-type HCT116 cells
2012-08-13 | E-GEOD-31126 | biostudies-arrayexpress
Project description:Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are critical to oncogenesis. The exact mechanism by which mutant IDH1 drives cell transformation is still not fully understood, partially due to the difficulty of maintaining cells with endogenously mutated IDH1. We employed a “single base editing” technique and efficiently introduced the monoallelic point mutation of IDH1 R132H (IDH1R132H/WT) into non-neoplastic human astroglial cells. Characterization of our cellular models revealed that IDH1R132H/WT inhibited cell proliferation and promoted cell migration via mechanisms mediated by its oncometabolite 2-HG. Global gene expression and epigenetic analysis identified novel molecular targets of IDH1R132H/WT, namely the Hippo pathway effector, Yes-associated protein (YAP), and its downstream signaling pathway Notch. In summary, the “single base editing” strategy introduces a new paradigm that recapitulates the biological function of IDH1 R132H/WT and its oncometabolite 2-HG, which can be easily applied to other cell models. Our study provides a valuable model for novel discoveries of molecular mechanisms during IDH1 R132H/WT-driven pre-cancerous events.
2018-06-01 | GSE103557 | GEO
Project description:Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are critical to oncogenesis. The exact mechanism by which mutant IDH1 drives cell transformation is still not fully understood, partially due to the difficulty of maintaining cells with endogenously mutated IDH1. We employed a “single base editing” technique and efficiently introduced the monoallelic point mutation of IDH1 R132H (IDH1R132H/WT) into non-neoplastic human astroglial cells. Characterization of our cellular models revealed that IDH1R132H/WT inhibited cell proliferation and promoted cell migration via mechanisms mediated by its oncometabolite 2-HG. Global gene expression and epigenetic analysis identified novel molecular targets of IDH1R132H/WT, namely the Hippo pathway effector, Yes-associated protein (YAP), and its downstream signaling pathway Notch. In summary, the “single base editing” strategy introduces a new paradigm that recapitulates the biological function of IDH1 R132H/WT and its oncometabolite 2-HG, which can be easily applied to other cell models. Our study provides a valuable model for novel discoveries of molecular mechanisms during IDH1 R132H/WT-driven pre-cancerous events.
2018-06-01 | GSE103556 | GEO
Project description:To investigate whether IDH1 mutation influence the effects of oncolytic virus VSVΔ51, we transduced doxycycline-inducible IDH1-R132H lentiviruses into LN-229 to establish the LN-229-TRE-R132H cell line. We then performed gene expression profiling analysis using data obtained from RNA-seq of LN-229-TRE-R132H cells infected with or without VSVΔ51 in the presence or absence of IDH1 mutation induced by doxycycline.
2023-09-19 | GSE208634 | GEO
Project description:SJGBM2 and MGG8 glioma cells were stable transfected with IDH1-R132H mutated. The expression of IDH1-R132H was confirmed by Western Blot assay. The aim of this project is analyze the production of 2HG in the stable transfected cells (SJGBM-IDH1m and MGG8-IDH1m) compared with the control group WT.
2017-07-14 | ST000824 | MetabolomicsWorkbench