MiR-145 reduces ADAM17 expression and inhibits in vitro migration and             invasion of glioma cells.
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.
Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA.
Yong
Y
Lu
Michael
M
Chopp
Xuguang
X
Zheng
Mark
M
Katakowski
Benjamin
B
Buller
Feng
F
Jiang
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072198:ADAM17 Protein; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases; C512478:EGFR protein, human; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human