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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-06

AUTHORS

M Garofalo, C Quintavalle, G Di Leva, C Zanca, G Romano, C Taccioli, C G Liu, C M Croce, G Condorelli

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 p27(kip1) mRNAs, but interfere with TRAIL signaling mainly through p27(kip1). 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. More... »

PAGES

3845

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2008.6

DOI

http://dx.doi.org/10.1038/onc.2008.6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016943266

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18246122


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