Abstract
Hepatocellular carcinoma (HCC) ranks third in cancer-related mortality due to late diagnosis and poor treatment options. Autophagy is a lysosome-mediated protein and organelle degradation process which is characterized by the formation of double-membrane vesicles, known as autophagosomes. Increasing evidence reveals that autophagy functions as a survival mechanism in liver cancer cells against drug-induced apoptosis. In this study, we found that autophagy was suppressed by miR-101 in the HCC cell line HepG2. miR-101 inhibited autophagy via targets including RAB5A, STMN1 and ATG4D. Moreover, miR-101 enhanced apoptosis induced by cisplatin in the HepG2 cell line. The possible mechanism of this effect may be through inhibition of autophagy. Our results indicate a novel and critical role for miR-101 and autophagy in the chemoresistance of cisplatin in HCC. We propose that gene therapy targeting miR-101/autophagy should be investigated further as a potential alternative therapeutic strategy for HCC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / genetics*
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Autophagy / drug effects
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Autophagy / genetics*
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Autophagy-Related Proteins
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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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Carcinoma, Hepatocellular / pathology
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Cell Line, Tumor
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Cisplatin / pharmacology*
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism
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Hep G2 Cells
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Humans
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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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Liver Neoplasms / pathology
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MicroRNAs / genetics*
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MicroRNAs / metabolism*
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Stathmin / genetics
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Stathmin / metabolism
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism
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rab5 GTP-Binding Proteins / genetics
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rab5 GTP-Binding Proteins / metabolism
Substances
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Autophagy-Related Proteins
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MIRN101 microRNA, human
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MicroRNAs
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STMN1 protein, human
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Stathmin
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MTOR protein, human
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TOR Serine-Threonine Kinases
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ATG4D protein, human
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Cysteine Endopeptidases
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rab5 GTP-Binding Proteins
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Cisplatin