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microRNA-7 Inhibits the Epidermal Growth Factor Receptor and the Akt Pathway and Is Down-regulated in Glioblastoma

¹ Division of Neuro-Oncology, Neurology Department, University of Virginia Health System, Charlottesville, Virginia; ² Dardinger Laboratory for Neuro-Oncology and Neurosciences, Department of Neurological Surgery, Ohio State University Medical Center, Columbus, Ohio; and ³ Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Benjamin Purow, University of Virginia Neuro-Oncology Center, Box 800434, Hospital West Complex 6th Floor, Charlottesville, VA 22908. Phone: 434-924-5545; Fax: 434-243-6843; E-mail: bwp5g{at}virginia.edu.

Key Words: microRNA • EGFR • Akt • glioblastoma • microRNA-7

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. [Cancer Res 2008;68(10):3566–71]