title: miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222.
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.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: M
authors.initials: M
authors.lastname: Acunzo
authors.forename: R
authors.initials: R
authors.lastname: Visone
authors.forename: G
authors.initials: G
authors.lastname: Romano
authors.forename: A
authors.initials: A
authors.lastname: Veronese
authors.forename: F
authors.initials: F
authors.lastname: Lovat
authors.forename: D
authors.initials: D
authors.lastname: Palmieri
authors.forename: A
authors.initials: A
authors.lastname: Bottoni
authors.forename: M
authors.initials: M
authors.lastname: Garofalo
authors.forename: P
authors.initials: P
authors.lastname: Gasparini
authors.forename: G
authors.initials: G
authors.lastname: Condorelli
authors.forename: M
authors.initials: M
authors.lastname: Chiariello
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D009842:Oligopeptides / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D020413:3' Untranslated Regions; D015853:Cysteine Proteinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D035683:MicroRNAs; D009842:Oligopeptides; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met; D053221:TNF-Related Apoptosis-Inducing Ligand; C000715470:MAS1 protein, human; C554019:MIRN130 microRNA, human; C525709:MIR221, human; C525710:MIR222, human; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; C491743:MET protein, human