TY - JOUR
T1 - In vivo activity of MiR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs) against multiple myeloma
AU - Di Martino, Maria Teresa
AU - Campani, Virginia
AU - Misso, Gabriella
AU - Gallo Cantafio, Maria Eugenia
AU - Gullà, Annamaria
AU - Foresta, Umberto
AU - Guzzi, Pietro Hiram
AU - Castellano, Maria
AU - Grimaldi, Anna
AU - Gigantino, Vincenzo
AU - Franco, Renato
AU - Lusa, Sara
AU - Cannataro, Mario
AU - Tagliaferri, Pierosandro
AU - De Rosa, Giuseppe
AU - Tassone, Pierfrancesco
AU - Caraglia, Michele
PY - 2014/2/27
Y1 - 2014/2/27
N2 - 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
AB - 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
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U2 - 10.1371/journal.pone.0090005
DO - 10.1371/journal.pone.0090005
M3 - Article
C2 - 24587182
AN - SCOPUS:84897872063
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e90005
ER -