MiR-145 reduces ADAM17 expression and inhibits in vitro migration and invasion of glioma cells

Lu,Yong; Chopp,Michael; Zheng,Xuguang; Katakowski,Mark; Buller,Benjamin; Jiang,Feng

doi:10.3892/or.2012.2084

MiR-145 reduces ADAM17 expression and inhibits in vitro migration and invasion of glioma cells

Authors:
- Yong Lu
- Michael Chopp
- Xuguang Zheng
- Mark Katakowski
- Benjamin Buller
- Feng Jiang
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Affiliations: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA
Published online on: October 17, 2012 https://doi.org/10.3892/or.2012.2084
Pages: 67-72

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Abstract

MicroRNAs are important regulators of gene expression and have been suggested to play a key role in tumorigenesis. In this study, we show that miR-145 is significantly downregulated in glioma cell lines compared to normal brain tissue and negatively regulates tumorigenesis. Restoration of miR-145 in glioma cells significantly reduced in vitro proliferation, migration and invasion. Also, overexpression of miR-145 reduced ADAM17 and EGFR expression. In addition, we tested the hypothesis that the miR-145-mediated suppression of cell proliferation, migration and invasion is, at least in part, due to silencing of ADAM17 and EGFR gene expression. Using luciferase reporters carrying the 3'-untranslated region of ADAM17 combined with western blotting, we identified ADAM17 as a direct target of miR-145. Collectively, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor proliferation, but also cell migration and invasion, and warrants further investigation.

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