PLX188109

GSE103557: Expression profiles in wild-type and IDH1 R132H/WT human astroglial cells [RNA-seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

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. SOURCE: Jie Wang (jwang240@jhmi.edu) - Johns Hopkins University