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

microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma
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DOI:
10.1158/0008-5472.can-07-6639
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发表时间:
2008-05-15
期刊:
影响因子:
11.2
通讯作者:
Purow, Benjamin
Purow, Benjamin
中科院分区:
医学1区
文献类型:
--
作者:
Kefas, Benjamin;Godlewski, Jakub;Purow, Benjamin

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microRNA是抑制许多靶基因表达的非编码RNA,并且一些已被证明作为致癌基因或肿瘤抑制因子。我们发现microRNA-7(miR-7)是胶质母细胞瘤中靶向关键癌症通路的潜在肿瘤抑制因子。miR-7有效地抑制表皮生长因子受体的表达,而且它通过靶向上游调控因子独立地抑制Akt通路。miR-7表达在胶质母细胞瘤与周围脑中下调,其机制涉及受损的加工。重要的是,用miR-7转染降低了原代胶质母细胞瘤细胞系的活力和侵袭性。这项研究确立了miR-7作为主要癌症途径的调节因子,并表明它对胶质母细胞瘤具有治疗潜力。
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.