ELF1 upregulates MEIS1 to accelerate proliferation, migration and invasion of glioma cells through the GFI1/FBW7 axis

Abstract Background: To explore whether the transcription factor ELF1 affects the GFI1-FBW7 through MEIS1, thus participating in the occurrence and development of glioma. In this study, key transcription factors were identified by differential analysis of GEO database, and downstream regulatory pathways were predicted by available literature.Methods and results: Based on bioinformatics analysis and existing studies, we speculate that the transcription factor ELF1 may regulate FBW7 through MEIS1-mediated GFI1 and thus affect the occurrence of glioma. The expressions of transcription factors ELF1, MEIS1 and GFI1 were up-regulated in glioma tissues, and the prognosis of glioma patients with high expression of ELF1 was worse.We found that interfering with ELF1 expression in glioma cells can reduce the proliferation, migration and invasion of tumor cells and induce cell apoptosis. The results of Western-blot showed that the expressions of PCNA and MMP9 were decreased, while the expression of cleaved caspase-3 was up-regulated. ChIP experiments showed that ELF1 binds to the MEIS1 promoter region, and MEIS1 can activate the enhancer of GFI1. In vivo experiments were carried out in nude mice, the results showed that interfering ELF1 could inhibit tumor growth in nude mice through the MEIS1-GFI1/FBW7.Conclusion: Therefore, interference of ELF1 in glioma can reduce its ability to recruit the transcription factor MEIS1, and further impair the activation ability of MEIS1 to GFI1 enhancer, which resulting in suppression of proliferation, migration and invasion and induction of cell apoptosis in glioma cells.