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miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222

Oncogene volume 31, pages 634–642 (2012)Cite this article

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 p27kip1, 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.

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Acknowledgements

This study was supported by the NCI grants to (CMC) and Associazione Italiana Ricerca sul Cancro, AIRC grant to GC.

We thank Veronica Balatti, Giampiero di Leva, Claudia Piovan, Hansjuerg Alder and Paolo Fadda for the helpful discussions about this manuscript.

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Authors and Affiliations

  1. Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA

    M Acunzo, R Visone, A Veronese, F Lovat, D Palmieri, A Bottoni, M Garofalo, P Gasparini & C M Croce

  2. Fondazione IRCCS SDN, Naples, Italy

    G Romano

  3. Department of Cellular and Molecular Biology and Pathology, Istituto di Endocrinologia e Oncologia Sperimentale ‘G. Salvatore’—Consiglio Nazionale delle Ricerche, Faculty of Biotechnological Science, ‘Federico II’ University of Naples, Naples, Italy

    D Palmieri & G Condorelli

  4. Istituto Toscano Tumori (ITT) and Istituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche (IFC_CNR), Siena, Italy

    M Chiariello

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  1. M Acunzo
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  2. R Visone
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  3. G Romano
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  11. M Chiariello
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Correspondence to C M Croce.

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Acunzo, M., Visone, R., Romano, G. et al. miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222. Oncogene 31, 634–642 (2012). https://doi.org/10.1038/onc.2011.260

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  • DOI: https://doi.org/10.1038/onc.2011.260

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