Antagomir-17-5p Abolishes the Growth of Therapy-resistant Neuroblastoma Through P21 and BIM

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 May 22

PMID 18493594

Citations 190

Authors

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

Affiliations

Soon will be listed here.

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 translation 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 antagomir-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.

Citing Articles

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