miR-579-3p controls melanoma progression and resistance to target therapy

Fattore Luigi; Mancini Rita; Acunzo MarioRomano GiuliaLagana AlessandroPisanu Maria ElenaMalpicci DeboraMadonna GabrieleMallardo DomenicoCapone MarilenaFulciniti FrancoMazzucchelli LucaBotti GerardoCroce Carlo M.Ascierto Paolo AntonioCiliberto Gennaro

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miR-579-3p controls melanoma progression and resistance to target therapy

机译：miR-579-3p controls melanoma progression and resistance to target therapy

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Therapy of melanoma patients harboring activating mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) oncogene with a combination of BRAF and MEK inhibitors is plagued by the development of drug resistance. Mutational events, as well as adaptive mechanisms, contribute to the development of drug resistance. In this context we uncover here the role of a miRNA, miR-579-3p. We first show that lowexpression ofmiR-579-3p is a negative prognostic factor correlating with poor survival. Expression levels of miR-579-3p decrease from nevi to stage III/IV melanoma samples and even further in cell lines resistant to BRAF/MEK inhibitors. Mechanistically, we demonstrate that miR-579-3p acts as an oncosuppressor by targeting the 3'UTR of two oncoproteins: BRAF and an E3 ubiquitin protein ligase, MDM2. Moreover miR-579-3p ectopic expression impairs the establishment of drug resistance in human melanoma cells. Finally, miR-579-3p is strongly down-regulated in matched tumor samples from patients before and after the development of resistance to targeted therapies.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2016年第34期|E5005-E5013|共9页
作者
Fattore Luigi; Mancini Rita; Acunzo MarioRomano GiuliaLagana AlessandroPisanu Maria ElenaMalpicci DeboraMadonna GabrieleMallardo DomenicoCapone MarilenaFulciniti FrancoMazzucchelli LucaBotti GerardoCroce Carlo M.Ascierto Paolo AntonioCiliberto Gennaro;
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作者单位

Ist Nazl Studio & Cura Tumori, Fdn G Pascal, I-80131 Naples, Italy;

Sapienza Univ Roma, Dipartimento Med Clin & Mol, I-00161 Rome, Italy;

Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USAIcahn Sch Med Mt Sinai, Dept Genet, Genom Sci, New York, NY 10029 USAUniv Catanzaro Magna Graecia, Dipartimento Med Sperimentale & Clin, I-88100 Catanzaro, ItalyIst Cantonale Patol, Serv Citol Clin, CH-6600 Locarno, Switzerland;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
miRNA; melanoma; targeted therapy; drug resistance;

miR-579-3p controls melanoma progression and resistance to target therapy

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