Abstract
CDK2 is a key regulator of cell cycle progression. In this study, we screened for miRNAs targeting CDK2 using a luciferase-3'-untranslated region reporter assay. Among 11 hit miRNAs, miR-509-3p reduced CDK2 protein levels and significantly inhibited cancer cell growth. Microarray, Western blotting, and luciferase reporter analyses revealed additional targets of miR-509-3p, including Rac1 and PIK3C2A. Overexpression of miR-509-3p induced G1 cell-cycle arrest and inhibited colony formation and migration. RNAi experiments indicated that the growth-inhibitory effects of miR-509-3p may occur through down-regulation of CDK2, Rac1, and PIK3C2A. Targeting of multiple growth regulatory genes by miR-509-3p may contribute to effective anti-cancer therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Cycle / genetics
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Cell Movement / genetics
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Cell Proliferation / genetics
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Cyclin-Dependent Kinase 2 / genetics
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Cyclin-Dependent Kinase 2 / metabolism*
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Down-Regulation / genetics
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HeLa Cells
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Humans
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Microarray Analysis
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Neoplasms / genetics
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Neoplasms / therapy*
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Neoplastic Stem Cells
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism*
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RNA, Small Interfering / genetics
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Transgenes / genetics
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rac1 GTP-Binding Protein / genetics
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rac1 GTP-Binding Protein / metabolism*
Substances
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MIRN509 microRNA, human
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MicroRNAs
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RNA, Small Interfering
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Phosphatidylinositol 3-Kinases
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PIK3C2A protein, human
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Cyclin-Dependent Kinase 2
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rac1 GTP-Binding Protein