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

被引：234

作者：

Garofalo, M. ^{[1
,2
,3
]}

Quintavalle, C. ^{[1
,2
]}

Di Leva, G. ^{[3
]}

Zanca, C. ^{[1
,2
]}

Romano, G. ^{[1
,2
]}

Taccioli, C. ^{[3
]}

Liu, C. G. ^{[3
]}

Croce, C. M. ^{[3
]}

Condorelli, G. ^{[1
,2
,4
]}

机构：

[1] Univ Naples Federico 2, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy

[2] IEOS, CNR, Ist Endocrinol & Oncol Sperimentale, Naples, Italy

[3] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Human Canc Genet Program, Columbus, OH 43210 USA

[4] Univ Naples Federico 2, Fac Sci Biotecnol, I-80131 Naples, Italy

来源：

ONCOGENE | 2008年 / 27卷 / 27期

关键词：

microRNA; non-small cell lung cancer; apoptosis;

D O I：

10.1038/onc.2008.6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To de. ne 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 pro. ling 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 p27kip1. In conclusion, we showthat 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.

引用

页码：3845 / 3855

页数：11

共 39 条

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