Hypoxia-inducible factor 1α (HIF-1α)-activated Gli1 induces invasion and EMT by H3K4 methylation in glioma cells

Abstract Objectives Gliomas are highly aggressive neuroepithelial-layer malignancies. Hypoxia-inducible factor 1α (HIF-1α) was revealed to be upregulated in gliomas under hypoxia. Nevertheless, its role glioma cells remains elusive. We attempted clarify the molecular mechanism of HIF-1 underlying glioma. Methods Cellular models were established mimic characteristics RT‒qPCR used detect HIF-1α and Gli1 levels with or without hypoxic treatment. Transwell assays measure invasive ability U87 U251 cells. Western blotting evaluate epithelial-mesenchymal transition (EMT)-associated protein abundance H3K4 methylation (H3K4me)-associated ChIP assessed association H3K4me promoter Results relative normal human astrocytes (NHAs). also hypoxia-treated untreated Both silencing suppressed invasion EMT transcriptionally via MLL1-mediated H3K4me. mutation further demonstrated suppress cell Conclusions function as oncogenes activates cells, providing ideas for seeking new therapeutic directions