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MicroRNA-1298-3p inhibits proliferation and invasion of glioma cells by downregulating Nidogen-1

机译:MicroRNA-1298-3p通过下调Nidogen-1抑制神经胶质瘤细胞的增殖和侵袭

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摘要

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.
机译:神经胶质瘤是中枢神经系统最普遍的肿瘤。为了鉴定不同等级的神经胶质瘤中差异表达的miRNA(DEM),进行了生物信息学分析。通过使用LIMMA软件包筛选Gene Expression Omnibus和The Cancer Genome Atlas数据库,可以鉴定低度神经胶质瘤(LGG)和高度神经胶质瘤(HGG)之间的DEM。通过比较LGG和HGG,确定了六个重叠的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的增殖,迁移和侵袭。基底膜蛋白Nidogen-1(NID1)被确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NID1和波形蛋白的水平,但上调E-钙粘蛋白的水平。重要的是,miR-1298-3p的过度表达在神经胶质瘤的小鼠异种移植模型中诱导了细胞凋亡并降低了肿瘤的生长。我们的结果表明,miR-1298-3p在神经胶质瘤细胞中起着抑癌作用,并暗示它可能在神经胶质瘤患者中作为潜在的生物标志物和治疗靶标。

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