Abstract
Although genistein has been shown to inhibit tumorigenesis in a variety of human cancers including pancreatic cancer (PC), the exact molecular mechanism of its anti-cancer effects has not yet been fully elucidated. Recently, microRNAs (miRNAs) have been reported to regulate multiple aspects of tumor development and progression, indicating that targeting miRNAs could be a novel strategy to treat human cancers. In the current study, we investigated whether a natural compound genistein could down-regulate onco-miR-223, resulting in the inhibition of cell growth and invasion, and induction of apoptosis in PC cells. We found that genistein treatment significantly inhibited miR-223 expression and up-regulated Fbw7, one of the targets of miR-223. Moreover, down-regulation of miR-223 inhibited cell growth and induced apoptosis in PC cells. These findings suggest that genistein exerts its anti-tumor activity partly through downregulation of miR-223 in PC cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Apoptosis / genetics
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Cell Cycle / drug effects
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Cell Cycle / genetics
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Cell Cycle Proteins / genetics*
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Down-Regulation
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F-Box Proteins / genetics*
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F-Box Proteins / metabolism
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F-Box-WD Repeat-Containing Protein 7
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Gene Expression Regulation, Neoplastic / drug effects
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Genistein / pharmacology*
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Genistein / therapeutic use
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Humans
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MicroRNAs / genetics*
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MicroRNAs / metabolism*
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Pancreatic Neoplasms / drug therapy
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Pancreatic Neoplasms / genetics*
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Ubiquitin-Protein Ligases / genetics*
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Ubiquitin-Protein Ligases / metabolism
Substances
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Antineoplastic Agents
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Cell Cycle Proteins
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F-Box Proteins
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F-Box-WD Repeat-Containing Protein 7
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FBXW7 protein, human
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MIRN223 microRNA, human
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MicroRNAs
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Genistein
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Ubiquitin-Protein Ligases