E2F transcription factor 1 elevates cyclin D1 expression by suppressing transcription of microRNA-107 to augment progression of glioma.

Background: Dysregulation of microRNAs has been frequently implicated in the progression of human diseases, including glioma. This study aims to explore the interaction between E2F transcription factor 1 (E2F1) and miR-107 in the progression of glioma.

Methods: Expression of miR-107 in glioma tissues and cells was examined. Putative binding sites between E2F1 and the promoter region of miR-107, and between miR-107 and cyclin D1 (CCND1) mRNA were predicted via bioinformatic systems and validated via chromatin immunoprecipitation and luciferase reporter gene assays. Altered expression of miR-107, E2F1, and CCND1 was introduced in A172 and T98G cells to examine their roles in cell growth and the activity of the Wnt/β-catenin signaling. In vivo experiments were performed by injecting cells in nude mice.

Results: miR-107 was poorly expressed, whereas E2F1 and CCND1 were highly expressed in glioma tissues and cells. E2F1 bound to the promoter region of miR-107 to induce transcriptional repression, and miR-107 directly bound to CCND1 mRNA to reduce its expression. Overexpression of miR-107 reduced proliferation, migration and invasion, and augmented apoptosis of glioma cells, and it reduced activity of the Wnt/β-catenin pathway. The anti-tumorigenic roles of miR-107 were blocked by E2F1 or CCND1 overexpression. Similar results were reproduced in vivo where miR-107 overexpression or E2F1 inhibition blocked tumor growth in nude mice.

Conclusion: This study suggested that E2F1 reduces miR-107 transcription to induce CCND1 upregulation, which leads to progression of glioma via Wnt/β-catenin signaling activation.