Transcription factor ELF1 activates MEIS1 transcription and then regulates the GFI1/FBW7 axis to promote the development of glioma

Abstract Glioma is the most common malignancy in the central nervous system with no immediate prospect of a cure. Comprehensive understanding on the pathogenesis of the disorder contributes to better outcome. Herein, we aimed to investigate whether transcription factor ELF1, MEIS1 and GFI1/FBW7 mediates progression of glioma. ELF1, MEIS1 and GFI1 were upregulated in glioma cells and tissues as ELF1 was correlated to poor prognosis. Bioinformatics analysis identified the binding between ELF1 and MEIS1 as well as between GFI1 and FBW7, confirmed by ChIP experiment. Functional experiment indicated that silencing of ELT1 decreased MEIS1 expression and that overexpression of MEIS1 increased GFI1 expression by activating GFI1 enhancer but decreased FBW7 expression. Importantly, silencing of ELF1 decreased the capacities of proliferation, migration and invasion of glioma cells whereas increased apoptosis, supported by increased Capase-3 and decreased MMP-9 and PCNA expression. Moreover, in vivo experiment confirmed the inhibitory role of silenced ELF1 in tumor growth, with decreased level of MEIS1 and GFI1. Taken altogether, our study elucidated a potential mechanism that ELF1 promoted cell progression by increasing GFI1 and METS1 as well as decreasing FBW7 expression in glioma.