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Title:
MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer | Oncogene
Description:
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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name:Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, USA
name:Department of Cellular and Molecular Biology and Pathology, University of Naples Federico II, Naples, Italy
name:Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, IEOS, Naples, Italy
name:Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, USA
name:Department of Cellular and Molecular Biology and Pathology, University of Naples Federico II, Naples, Italy
name:Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, IEOS, Naples, Italy
name:Department of Cellular and Molecular Biology and Pathology, University of Naples Federico II, Naples, Italy
name:Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, IEOS, Naples, Italy
name:Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, USA
name:Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, USA
name:Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, USA
name:Department of Cellular and Molecular Biology and Pathology, University of Naples Federico II, Naples, Italy
name:Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, IEOS, Naples, Italy
name:Facoltà di Scienze Biotecnologiche, University of Naples Federico II, Naples, Italy
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