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

• Published in: Brain and behavior 2021-12, Vol.11 (12), p.e2399-n/a
• Main Authors: Xie, Huan, Lv, Shigang, Wang, Zhaozhen, Yuan, Xinzhang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Brain cancer; Brain research; Cancer therapies; Cell Line, Tumor; Cell Proliferation - genetics; cyclin D1; Cyclin D1 - genetics; Cyclin D1 - metabolism; E2F transcription factor 1; E2F Transcription Factors - metabolism; Genes; Glioma; Glioma - genetics; Glioma - pathology; Humans; Laboratory animals; Medical prognosis; Medical research; Mice; Mice, Nude; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐107; Original; Plasmids; Proteins; Transcription factors; Tumors; Wnt/β‐catenin
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.2399

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. By performing cellular and animal experiments, we confirmed that the transcription factor E2P1 can induce transcriptional repression of miR‐107 and block its inhibitory effect on CCND1, which leads to the malignant development of glioma with the involvement of the Wnt/β‐catenin signaling pathway. This study confirmed the oncogenic roles of E2F1 and CCND1 and the anti‐tumorigenic role of miR‐107 in glioma.