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Title[redir]:
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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Keywords {🔍}
article, google, scholar, cas, cancer, cell, nature, microrna, human, expression, apoptosis, trail, access, oncogene, lung, micrornas, pkip, content, resistance, cells, res, cookies, published, nonsmall, garofalo, condorelli, tumor, usa, privacy, quintavalle, romano, open, proc, natl, acad, sci, biol, protein, walczak, naples, data, february, signatures, leva, zanca, nsclc, mirs, levels, role, nat,
Topics {✒️}
nature portfolio permissions reprints privacy policy nature 432 nature advertising cancer development social media related apoptosis-inducing ligand author information authors p27 cell-cycle inhibitors micro-rna genes mir15 h460-sensitive cells treated author correspondence genome-wide microrna profiling circulating mir-22-3p levels tumor necrosis factor chronic lymphocytic leukemia personal data springerlink instant access trail-induced apoptosis pathway data protection permissions trail-resistant nsclc cells neural cell specification mir-222 expression affects erythroleukemic cell growth decreased cell proliferation privacy human dendritic cells european economic area issue learn papillary thyroid carcinoma calin ga increased p27kip1 expression molecular biology high expression levels caspase-induced proteolysis tumor suppressor gene genome-scale microrna human neuronal differentiation cyclin-cdk activity van de craen explore content subscription content comprehensive cancer center ohio state university trail-induced apoptosis key functional proteins promising therapeutic targets
Questions {❓}
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headline:MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer
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datePublished:2008-02-04T00:00:00Z
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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 3â²-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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