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MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells

¹ Neuroscience Research Institute and ² Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, California

Requests for reprints: Kenneth S. Kosik, UC Santa Barbara BLDG571, RM6129 Santa Barbara, CA 93106. Phone: 805-893-5222; Fax: 805-893-2005; E-mail: kosik{at}lifesci.ucsb.edu.

Key Words: MiR-21 • Glioblastoma • Cancer • microRNA • p53

MicroRNA dysregulation is observed in different types of cancer. MiR-21 up-regulation has been reported for the majority of cancers profiled to date; however, knowledge is limited on the mechanism of action of miR-21, including identification of functionally important targets that contribute to its proproliferative and antiapoptotic actions. In this study, we show for the first time that miR-21 targets multiple important components of the p53, transforming growth factor-β (TGF-β), and mitochondrial apoptosis tumor-suppressive pathways. Down-regulation of miR-21 in glioblastoma cells leads to derepression of these pathways, causing repression of growth, increased apoptosis, and cell cycle arrest. These phenotypes are dependent on two of the miR-21 targets validated in this study, HNRPK and TAp63. These findings establish miR-21 as an important oncogene that targets a network of p53, TGF-β, and mitochondrial apoptosis tumor suppressor genes in glioblastoma cells. [Cancer Res 2008;68(19):8164–72]

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