IDH1 mutation promotes proliferation and migration of glioma cells via EMT induction.

PURPOSE: To investigate whether IDH1 mutation or 2-hydroxyglutarate (2-HG), the oncometabolite produced by IDH mutations, is correlated to epithelial-mesenchymal transition (EMT)-like phenotype in glioma cells, so as to clarify how IDH1 mutation is good prognostic factor while 2-HG, being its oncometabolite, remains unknown. METHODS: U87 and T98 cell lines were treated with 10 mM exogenous 2-HG, and fresh 2-HG was replenished every 2-days intervals. Endogenously heterozygous mutation in IDH1 was generated via lentiviral transduction technology. Morphological analysis, wound healing assay and Boyden migration assay were used to detect the ability of migration of U87 and 2-HG-treated U87 cell lines, and immunoblotting was used to detect the EMT-related transcription factors in glioma cell line. RESULTS: Cellular morphology changed after IDH1 mutation and 2-HG stimulation. The Cell Counting Kit-8 assay, and wound healing assay showed that exogenous 2-HG promotes the proliferation and invasion of glioma cells. Western blot analysis showed that mesenchymal marker β-Catenin was increased in the exogenous 2-HG-treated and IDH1 mutated U87 cells, while epithelial markers E-cadherin and ZO1 were decreased. CONCLUSIONS: Our study showed some evidence that both IDH1 mutation and 2-HG can lead to EMT-like phenotype and proliferation and migration in glioma cells. EMT-like biomarkers changed in IDH1 mutation cells which generated via lentiviral transduction technology or treated in 2-HG.