In vivo activity of MiR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs) against multiple myeloma

Maria Teresa Di Martino, Virginia Campani, Gabriella Misso, Maria Eugenia Gallo Cantafio, Annamaria Gullà, Umberto Foresta, Pietro Hiram Guzzi, Maria Castellano, Anna Grimaldi, Vincenzo Gigantino, Renato Franco, Sara Lusa, Mario Cannataro, Pierosandro Tagliaferri, Giuseppe De Rosa, Pierfrancesco Tassone, Michele Caraglia

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple myeloma (MM) is a disease with an adverse outcome and new therapeutic strategies are urgently awaited. A rising body of evidence supports the notion that microRNAs (miRNAs), master regulators of eukaryotic gene expression, may exert anti-MM activity. Here, we evaluated the activity of synthetic miR-34a in MM cells. We found that transfection of miR-34a mimics in MM cells induces a significant change of gene expression with relevant effects on multiple signal transduction pathways. We detected early inactivation of pro-survival and proliferative kinases Erk-2 and Akt followed at later time points by caspase-6 and -3 activation and apoptosis induction. To improve the in vivo delivery, we encapsulated miR-34a mimics in stable nucleic acid lipid particles (SNALPs). We found that SNALPs miR-34a were highly efficient in vitro in inhibiting growth of MM cells. Then, we investigated the activity of the SNALPs miR-34a against MM xenografts in SCID mice. We observed significant tumor growth inhibition (p

Original languageEnglish
Article numbere90005
JournalPLoS One
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 27 2014

ASJC Scopus subject areas

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

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