microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma

被引:615
作者
Kefas, Benjamin [1 ]
Godlewski, Jakub [2 ]
Comeau, Laurey [1 ]
Li, Yunqing [1 ]
Abounader, Roger [1 ]
Hawkinson, Michael [1 ]
Lee, Jeongwu [3 ]
Fine, Howard [3 ]
Chiocca, E. Antonio [2 ]
Lawler, Sean [2 ]
Purow, Benjamin [1 ]
机构
[1] Univ Virginia Hlth Syst, Div Neurooncol, Dept Neurol, Charlottesville, VA USA
[2] Ohio State Univ, Dardinger Lab Neurooncol & Neurosci, Dept Neurol Surg, Columbus, OH 43210 USA
[3] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1158/0008-5472.CAN-07-6639
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
microRNAs are noncoding RNAs inhibiting expression of numerous target genes, and a few have been shown to act as oncogenes or tumor suppressors. We show that microRNA-7 (miR-7) is a potential tumor suppressor in glioblastoma targeting critical cancer pathways. miR-7 potently suppressed epidermal growth factor receptor expression, and furthermore it independently inhibited the Akt pathway via targeting upstream regulators. miR-7 expression was down-regulated in glioblastoma versus surrounding brain, with a mechanism involving impaired processing. Importantly, transfection with miR-7 decreased viability and invasiveness of primary glioblastoma lines. This study establishes miR-7 as a regulator of major cancer pathways and suggests that it has therapeutic potential for glioblastoma.
引用
收藏
页码:3566 / 3572
页数:7
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