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

• Published in: PloS one 2014-02, Vol.9 (2), p.e90005-e90005
• Main Authors: Di Martino, Maria Teresa, Campani, Virginia, Misso, Gabriella, Gallo Cantafio, Maria Eugenia, Gullà, Annamaria, Foresta, Umberto, Guzzi, Pietro Hiram, Castellano, Maria, Grimaldi, Anna, Gigantino, Vincenzo, Franco, Renato, Lusa, Sara, Cannataro, Mario, Tagliaferri, Pierosandro, De Rosa, Giuseppe, Tassone, Pierfrancesco, Caraglia, Michele
• Format: Article
• Language: English
• Subjects: Acids; AKT protein; Analysis; Animals; Apoptosis; Apoptosis - genetics; Biochemistry; Biocompatibility; Bioinformatics; Biology; Biophysics; Breast cancer; Caspase; Caspase-6; Caspases - metabolism; Cell Line, Tumor; Cell Survival - genetics; Cellular signal transduction; Clinical medicine; Cluster Analysis; College campuses; Deactivation; Disease Models, Animal; Ethanol; Extracellular signal-regulated kinase; Gene Expression; Gene Expression Profiling; Gene Transfer Techniques; Genes; Health aspects; Humans; Inactivation; Kinases; Laboratories; Lipids; Male; Medical research; Medicine; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; Multiple Myeloma - pathology; Nucleic acids; Oncology; Pathology; Pharmacy; Proto-Oncogene Proteins c-akt - metabolism; Regulators; Ribonucleic acid; RNA; Signal Transduction; Survival; Toxicity; Transcriptome; Transduction; Transfection; Tumors; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090005

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