Abstract
We investigated the role of microRNA (miR)-9 in modulating chemoresistance in hepatocellular carcinoma (HCC) cells. MiR-9 was overexpressed or knocked down in HCC cell lines. Cell viability, cell proliferation, the expression of EIF5A2 and the epithelial-mesenchymal transition (EMT)-related proteins were examined. HCC cells overexpressing miR-9 were more sensitive to cisplatin; miR-9 knockdown yielded the opposite result. The in vivo nude mouse HCC xenograft tumors yielded the same results. EIF5A2 was identified as a potential target of miR-9, where miR-9 regulated EIF5A2 expression at mRNA and protein level. EIF5A2 knockdown reversed miR-9 inhibition-mediated cisplatin resistance. Altering miR-9 and EIF5A2 expression changed E-cadherin and vimentin expression. Furthermore, EIF5A2 mediated miR-9 EMT pathway regulation, indicating that miR-9 can enhance cisplatin sensitivity by targeting EIF5A2 and inhibiting the EMT pathway. Targeting miR-9 may be useful for overcoming drug resistance in HCC.
Keywords:
EIF5A2; chemoresistance; epithelial-mesenchymal transition; miR-9.
© The author(s).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism*
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Movement / ethics
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Cell Proliferation / drug effects
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Cell Proliferation / genetics
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Cisplatin / therapeutic use*
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Epithelial-Mesenchymal Transition / genetics
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Epithelial-Mesenchymal Transition / physiology
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Eukaryotic Translation Initiation Factor 5A
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / genetics
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Humans
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Immunohistochemistry
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In Situ Nick-End Labeling
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism*
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Mice
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Mice, Nude
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Peptide Initiation Factors / genetics
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Peptide Initiation Factors / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
Substances
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MIRN92 microRNA, human
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MicroRNAs
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Peptide Initiation Factors
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RNA, Messenger
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RNA-Binding Proteins
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Cisplatin