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MiR-18a regulates the proliferation,migration and invasion of human glioblastoma cell by targeting neogenin
Authors:Yichen Song  Ping Wang  Wei Zhao  Yilong Yao  Xiaobai Liu  Jun Ma  Yixue Xue  Yunhui Liu
Institution:1. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People?s Republic of China;2. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, People?s Republic of China;3. Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, People?s Republic of China;4. The 96th Class, 7-year Program, China Medical University, Shenyang, Liaoning Province 110001, People?s Republic of China
Abstract:MiR-17-92 cluster has recently been reported as an oncogene in some tumors. However, the association of miR-18a, an important member of this cluster, with glioblastoma remains unknown. Therefore, this study aims to investigate the expression of miR-18a in glioblastoma and its role in biological behavior of U87 and U251 human glioblastoma cell lines. Quantitative RT-PCR results showed that miR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines compared with that in human brain tissues and primary normal human astrocytes, and the expression levels were increased along with the rising pathological grades of glioblastoma. Neogenin was identified as the target gene of miR-18a by dual-luciferase reporter assays. RT-PCR and western blot results showed that its expression levels were decreased along with the rising pathological grades of glioblastoma. Inhibition of miR-18a expression was established by transfecting exogenous miR-18a inhibitor into U87 and U251 cells, and its effects on the biological behavior of glioblastoma cells were studied using CCK-8 assay, transwell assay and flow cytometry. Inhibition of miR-18a expression in U87 and U251 cells significantly up-regulated neogenin, and dramatically suppressed the abilities of cell proliferation, migration and invasion, induced cell cycle arrest and promoted cellular apoptosis. Collectively, these results suggest that miR-18a may regulate biological behavior of human glioblastoma cells by targeting neogenin, and miR-18a can serve as a potential target in the treatment of glioblastoma.
Keywords:Glioblastoma  MiR-18a  Neogenin  Proliferation  Migration  Invasion
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