Department of Clinical Medicine, Jiangxi Health Vocational College, Nanchang, P. R. China.
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, P. R. China.
Brain Behav. 2021 Dec;11(12):e2399. doi: 10.1002/brb3.2399. Epub 2021 Nov 10.
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.
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.
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.
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.
microRNAs 的失调经常与包括神经胶质瘤在内的人类疾病的进展有关。本研究旨在探讨 E2F 转录因子 1（E2F1）与 miR-107 在神经胶质瘤进展中的相互作用。
检测 miR-107 在神经胶质瘤组织和细胞中的表达。通过生物信息学系统预测 E2F1 与 miR-107 启动子区域之间以及 miR-107 与细胞周期蛋白 D1（CCND1）mRNA 之间的假定结合位点，并通过染色质免疫沉淀和荧光素酶报告基因检测进行验证。在 A172 和 T98G 细胞中改变 miR-107、E2F1 和 CCND1 的表达，以研究它们在细胞生长和 Wnt/β-catenin 信号通路活性中的作用。通过向裸鼠注射细胞进行体内实验。
miR-107 在神经胶质瘤组织和细胞中表达水平较低，而 E2F1 和 CCND1 表达水平较高。E2F1 结合到 miR-107 的启动子区域，诱导转录抑制，miR-107 直接结合到 CCND1 mRNA 上，降低其表达。miR-107 的过表达减少了神经胶质瘤细胞的增殖、迁移和侵袭，并促进了细胞凋亡，同时降低了 Wnt/β-catenin 通路的活性。E2F1 或 CCND1 的过表达阻断了 miR-107 的抗肿瘤作用。在体内实验中也得到了类似的结果，miR-107 的过表达或 E2F1 的抑制阻断了裸鼠肿瘤的生长。
本研究表明，E2F1 降低 miR-107 的转录以诱导 CCND1 的上调，从而通过 Wnt/β-catenin 信号通路的激活导致神经胶质瘤的进展。
