Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM

Laura Fontana; Micol E. Fiori; Sonia Albini; Loredana Cifaldi; Serena Giovinazzi; Matteo Forloni; Renata Boldrini; Alberto Donfrancesco; Valentina Federici; Patrizio Giacomini; Cesare Peschle; Doriana Fruci

doi:10.1371/journal.pone.0002236

Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM

Laura Fontana, Micol E. Fiori, Sonia Albini, Loredana Cifaldi, Serena Giovinazzi, Matteo Forloni, Renata Boldrini, Alberto Donfrancesco, Valentina Federici, Patrizio Giacomini, Cesare Peschle, Doriana Fruci

Research output: Contribution to journal › Article › peer-review

Abstract

We identified a key oncogenic pathway underlying neuroblastoma progression: specifically, MYCN, expressed at elevated level, transactivates the miRNA 17-5p-92 cluster, which inhibits p21 and BIM translocation by interaction with their mRNA 3′ UTRs. Overexpression of miRNA 17-5p-92 cluster in MYCN-not-amplified neuroblastoma cells strongly augments their in vitro and in vivo tumorigenesis. In vitro or in vivo treatment with antagonis 17-5p abolishes the growth of MYCN amplified and therapy resistant neuroblastoma through p21 and BIM upmodulation, leading to cell cycling blockade and activation of apoptosis, respectively. In primary neuroblastoma, the majority of cases show a rise of miR-17-5p level leading to p21 downmodulation, which is particularly severe in patients with MYCN amplification and poor prognosis. Altogether, our studies demonstrate for the first time that antagomir treatment can abolish tumor growth in vivo, specifically in therapy resistant neuroblastoma.

Original language	English
Article number	e2236
Journal	PLoS One
Volume	3
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0002236
Publication status	Published - May 21 2008

ASJC Scopus subject areas

Agricultural and Biological Sciences(all)
Biochemistry, Genetics and Molecular Biology(all)
Medicine(all)

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Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. / Fontana, Laura; Fiori, Micol E.; Albini, Sonia; Cifaldi, Loredana; Giovinazzi, Serena; Forloni, Matteo; Boldrini, Renata; Donfrancesco, Alberto; Federici, Valentina; Giacomini, Patrizio; Peschle, Cesare; Fruci, Doriana.

In: PLoS One, Vol. 3, No. 5, e2236, 21.05.2008.

Research output: Contribution to journal › Article › peer-review

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AU - Giovinazzi, Serena

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AU - Donfrancesco, Alberto

AU - Federici, Valentina

AU - Giacomini, Patrizio

AU - Peschle, Cesare

AU - Fruci, Doriana

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