Abstract
MicroRNAs (miRNA) have emerged as key players in carcinogenesis. Here, we investigated the role of miR-137 in the pathogenesis of lung cancer. The downregulation of miR-137 in lung cancer cells could be rescued following inhibition of DNA methylation. Ectopic expression of miR-137 in lung cancer cells significantly downregulated Cdc42, Cdk6 and induced G1 cell cycle arrest, leading to a significant decrease in cell growth in vivo and in vitro. Further, both Cdc42 and Cdk6 were confirmed as targets of miR-137.
Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / therapy
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Cell Line, Tumor
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Cell Proliferation
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Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
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Cyclin-Dependent Kinase 6 / genetics
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Cyclin-Dependent Kinase 6 / metabolism
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DNA Modification Methylases / antagonists & inhibitors
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Down-Regulation*
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G1 Phase / drug effects
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Gene Expression Regulation, Neoplastic
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Gene Silencing
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Gene Transfer Techniques
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Histone Deacetylase Inhibitors / pharmacology
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Humans
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Lung / drug effects
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Lung / metabolism*
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Lung Neoplasms / drug therapy
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Lung Neoplasms / metabolism*
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Lung Neoplasms / therapy
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Mice
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Xenograft Model Antitumor Assays
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cdc42 GTP-Binding Protein / antagonists & inhibitors*
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cdc42 GTP-Binding Protein / genetics
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cdc42 GTP-Binding Protein / metabolism
Substances
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Antineoplastic Agents
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Histone Deacetylase Inhibitors
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MIRN137 microRNA, human
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MIRN137 microRNA, mouse
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MicroRNAs
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DNA Modification Methylases
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CDK6 protein, human
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Cdk6 protein, mouse
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Cyclin-Dependent Kinase 6
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cdc42 GTP-Binding Protein