Abstract
Several miRNAs have been implicated in the development and progression of osteosarcoma (OS). In this study, we found that miR-16 is downregulated in OS cell lines and tissues. Overexpression of miR-16 suppresses OS cell proliferation and tumor growth in nude mice. Furthermore, we confirmed that IGF1R is a direct target of miR-16. Mechanistic investigation revealed that miR-16 overexpression inhibits the Raf1-MEK1/2-ERK1/2 pathway. In clinical specimens, IGF1R levels inversely correlate with miR-16 expression. Our results provide significant clues regarding the role of miR-16 as a tumor suppressor by targeting IGF1R in OS.
Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
MeSH terms
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Animals
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Base Sequence
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Cell Line, Tumor
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Cell Proliferation
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Down-Regulation / genetics
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Humans
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MAP Kinase Kinase 1 / metabolism
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MAP Kinase Kinase 2 / metabolism
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MAP Kinase Signaling System / genetics*
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Male
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Mice
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Mice, Inbred BALB C
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MicroRNAs / genetics*
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MicroRNAs / metabolism*
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Osteosarcoma / genetics
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Osteosarcoma / pathology*
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Proto-Oncogene Proteins c-raf / metabolism
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Receptor, IGF Type 1 / genetics*
Substances
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MIRN16 microRNA, human
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MicroRNAs
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MAP2K2 protein, human
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Receptor, IGF Type 1
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Proto-Oncogene Proteins c-raf
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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MAP Kinase Kinase 1
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MAP Kinase Kinase 2