Abstract
Non-small cell lung cancer (NSCLC) accounts for ∼80% of all lung cancers. Although some advances in lung cancer therapy have been made, patient survival is still quite poor. Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF-related apoptosis-inducing ligand (TRAIL) resistance in NSCLC cell lines, through the downregulation of p27(kip1), PTEN and TIMP3. Here, we further investigated this pathway and showed that miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in NSCLC cells through the c-Jun-mediated downregulation of miR-221 and miR-222. Moreover, we found that miR-130a reduced migratory capacity of NSCLC. A better understanding of MET-miR-221 and 222 axis regulation in drug resistance is the key in developing new strategies in NSCLC therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Apoptosis / drug effects
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Apoptosis / genetics
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Binding Sites / genetics
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Blotting, Western
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Movement / genetics
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Cell Survival / drug effects
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Cell Survival / genetics
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Cysteine Proteinase Inhibitors / pharmacology
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Down-Regulation
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Drug Resistance, Neoplasm / genetics
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Gene Expression Regulation, Neoplastic
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Humans
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JNK Mitogen-Activated Protein Kinases / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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MicroRNAs / genetics*
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Mutation
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Oligopeptides / pharmacology
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-met / genetics*
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Proto-Oncogene Proteins c-met / metabolism
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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TNF-Related Apoptosis-Inducing Ligand / pharmacology*
Substances
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3' Untranslated Regions
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Cysteine Proteinase Inhibitors
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MAS1 protein, human
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MIRN130 microRNA, human
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MIRN221 microRNA, human
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MIRN222 microRNA, human
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MicroRNAs
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Oligopeptides
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Proto-Oncogene Mas
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TNF-Related Apoptosis-Inducing Ligand
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benzyloxycarbonyl-valyl-alanyl-aspartic acid
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MET protein, human
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Proto-Oncogene Proteins c-met
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JNK Mitogen-Activated Protein Kinases