Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, P.R. China.
Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, P.R. China.
Aging (Albany NY). 2020 Apr 30;12(9):7761-7773. doi: 10.18632/aging.103087.
Glioma is the most prevalent tumor of the central nervous system. To identify differentially expressed miRNAs (DEMs) in gliomas of different grades, bioinformatics analysis was performed. The DEMs between low-grade gliomas (LGGs) and high-grade gliomas (HGGs) were identified by screening the Gene Expression Omnibus and The Cancer Genome Atlas databases using the LIMMA package. Six overlapping DEMs were identified by comparing LGGs and HGGs. Downregulation of miR-1298-3p correlated with poor overall survival rates in glioma patients. Overexpression of miR-1298-3p induced apoptosis of glioma cells and inhibited glioma cell proliferation, migration, and invasion. The basement membrane protein Nidogen-1 (NID1) was identified as a direct binding target of miR-1298-3p in glioma cells. MiR-1298-3p agonist downregulated the NID1 and vimentin levels, but upregulated the level of E-cadherin in glioma cells. Importantly, overexpression of miR-1298-3p induced apoptosis and reduced tumor growth in a mouse xenograft model of glioma. Our results show that miR-1298-3p functions as a tumor suppressor in glioma cells, and suggest that it might serve as a potential biomarker and therapeutic target in glioma patients.
神经胶质瘤是中枢神经系统最常见的肿瘤。为了鉴定不同级别神经胶质瘤中的差异表达 miRNA(DEM),我们进行了生物信息学分析。通过使用 LIMMA 程序包筛选基因表达综合数据库和癌症基因组图谱数据库,鉴定出低级别神经胶质瘤(LGG)和高级别神经胶质瘤(HGG)之间的 DEM。通过比较 LGG 和 HGG,鉴定出 6 个重叠的 DEM。miR-1298-3p 的下调与神经胶质瘤患者的总体生存率降低相关。miR-1298-3p 的过表达诱导神经胶质瘤细胞凋亡并抑制神经胶质瘤细胞增殖、迁移和侵袭。基底膜蛋白巢蛋白-1(NID1)被鉴定为神经胶质瘤细胞中 miR-1298-3p 的直接结合靶标。miR-1298-3p 激动剂下调神经胶质瘤细胞中的 NID1 和波形蛋白水平,但上调 E-钙黏蛋白水平。重要的是,miR-1298-3p 的过表达在神经胶质瘤的小鼠异种移植模型中诱导细胞凋亡并减少肿瘤生长。我们的研究结果表明,miR-1298-3p 在神经胶质瘤细胞中作为肿瘤抑制因子发挥作用,并提示其可能作为神经胶质瘤患者的潜在生物标志物和治疗靶标。