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MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer

Oncogene volume 27, pages 3845–3855 (2008)Cite this article

An Editorial Expression of Concern to this article was published on 28 February 2024

A Correction to this article was published on 04 January 2021

This article has been updated

Abstract

To define novel pathways that regulate susceptibility to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in non-small cell lung cancer (NSCLC), we have performed genome-wide expression profiling of microRNAs (miRs). We show that in TRAIL-resistant NSCLC cells, levels of different miRs are increased, and in particular, miR-221 and -222. We demonstrate that these miRs impair TRAIL-dependent apoptosis by inhibiting the expression of key functional proteins. Indeed, transfection with anti-miR-221 and -222 rendered CALU-1-resistant cells sensitive to TRAIL. Conversely, H460-sensitive cells treated with -221 and -222 pre-miRs become resistant to TRAIL. miR-221 and -222 target the 3′-UTR of Kit and p27kip1 mRNAs, but interfere with TRAIL signaling mainly through p27kip1. In conclusion, we show that high expression levels of miR-221 and -222 are needed to maintain the TRAIL-resistant phenotype, thus making these miRs as promising therapeutic targets or diagnostic tool for TRAIL resistance in NSCLC.

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Acknowledgements

This work was partially supported by funds from Associazione Italiana Ricerca sul Cancro, AIRC (GC), MIUR-FIRB (RBIN04J4J7), EU grant EMIL (European Molecular Imaging Laboratories Network) contract No. 503569. CQ is a recipient of Clinica Mediterranea Training program. GR is the recipient of SDN fellowship. We thank Dr Vittorio de Franciscis, Michael Latronico and Stefan Costinean for revision of this paper.

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Authors and Affiliations

  1. Department of Cellular and Molecular Biology and Pathology, University of Naples Federico II, Naples, Italy

    M Garofalo, C Quintavalle, C Zanca, G Romano & G Condorelli

  2. Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, IEOS, Naples, Italy

    M Garofalo, C Quintavalle, C Zanca, G Romano & G Condorelli

  3. Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    M Garofalo, G Di Leva, C Taccioli, C G Liu & C M Croce

  4. Facoltà di Scienze Biotecnologiche, University of Naples Federico II, Naples, Italy

    G Condorelli

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  1. M Garofalo
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  2. C Quintavalle
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Correspondence to G Condorelli.

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Garofalo, M., Quintavalle, C., Di Leva, G. et al. MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene 27, 3845–3855 (2008). https://doi.org/10.1038/onc.2008.6

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