In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma

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 synth...

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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:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937395/

id	pubmed-3937395
recordtype	oai_dc
spelling	pubmed-39373952014-03-04 In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma 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 Research Article 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<0.05) which translated in mice survival benefits (p = 0.0047). Analysis of miR-34a and NOTCH1 expression in tumor retrieved from animal demonstrated efficient delivery and gene modulation induced by SNALPs miR-34a in the absence of systemic toxicity. We here therefore provide evidence that SNALPs miR-34a may represent a promising tool for miRNA-therapeutics in MM. Public Library of Science 2014-02-27 /pmc/articles/PMC3937395/ /pubmed/24587182 http://dx.doi.org/10.1371/journal.pone.0090005 Text en © 2014 Di Martino et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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
spellingShingle	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 In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma
author_facet	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
author_sort	Di Martino, Maria Teresa
title	In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma
title_short	In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma
title_full	In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma
title_fullStr	In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma
title_full_unstemmed	In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma
title_sort	in vivo activity of mir-34a mimics delivered by stable nucleic acid lipid particles (snalps) against multiple myeloma
description	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<0.05) which translated in mice survival benefits (p = 0.0047). Analysis of miR-34a and NOTCH1 expression in tumor retrieved from animal demonstrated efficient delivery and gene modulation induced by SNALPs miR-34a in the absence of systemic toxicity. We here therefore provide evidence that SNALPs miR-34a may represent a promising tool for miRNA-therapeutics in MM.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937395/
_version_	1612062823532199936

In Vivo Activity of MiR-34a Mimics Delivered by Stable Nucleic Acid Lipid Particles (SNALPs) against Multiple Myeloma

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