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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3937395?pdf=render |
| _version_ | 1818853923319971840 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Maria Teresa Di Martino |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T07:44:31Z |
| format | Article |
| id | doaj.art-0957e6cd583246edb275f67115d5f29c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T07:44:31Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0957e6cd583246edb275f67115d5f29c2022-12-21T20:30:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e9000510.1371/journal.pone.0090005In vivo activity of miR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs) against multiple myeloma.Maria Teresa Di MartinoVirginia CampaniGabriella MissoMaria Eugenia Gallo CantafioAnnamaria GullàUmberto ForestaPietro Hiram GuzziMaria CastellanoAnna GrimaldiVincenzo GigantinoRenato FrancoSara LusaMario CannataroPierosandro TagliaferriGiuseppe De RosaPierfrancesco TassoneMichele CaragliaMultiple 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.http://europepmc.org/articles/PMC3937395?pdf=render |
| spellingShingle | 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 In vivo activity of miR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs) against multiple myeloma. PLoS ONE |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC3937395?pdf=render |
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