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MicroRNA therapeutics: design of single-stranded miR-216b mimics to target KRAS in pancreatic cancer cells.
Ferino, Annalisa; Miglietta, Giulia; Picco, Raffaella; Vogel, Stefan; Wengel, Jesper; Xodo, Luigi E.
Afiliación
  • Ferino A; a Department of Medicine, Laboratory of Biochemistry , University of Udine , Italy.
  • Miglietta G; a Department of Medicine, Laboratory of Biochemistry , University of Udine , Italy.
  • Picco R; a Department of Medicine, Laboratory of Biochemistry , University of Udine , Italy.
  • Vogel S; b Nucleic Acids Centre , University of Southern Denmark , Odense , Denmark.
  • Wengel J; b Nucleic Acids Centre , University of Southern Denmark , Odense , Denmark.
  • Xodo LE; a Department of Medicine, Laboratory of Biochemistry , University of Udine , Italy.
RNA Biol ; 15(10): 1273-1285, 2018.
Article en En | MEDLINE | ID: mdl-30306823
Datasets reporting microRNA expression profiles in normal and cancer cells show that miR-216b is aberrantly downregulated in pancreatic ductal adenocarcinoma (PDAC). We found that KRAS, whose mutant G12D allele drives the pathogenesis of PDAC, is a target of miR-216b. To suppress oncogenic KRAS in PDAC cells, we designed single-stranded (ss) miR-216b mimics with unlocked nucleic acid (UNA) modifications to enhance their nuclease resistance. We prepared variants of ss-miR-216b mimics with and without a 5' phosphate group. Both variants strongly suppressed oncogenic KRAS in PDAC cells and inhibited colony formation in pancreatic cancer cells. We observed that the designed ss-miR-216b mimics engaged AGO2 to promote the silencing of KRAS. We also tested a new delivery strategy based on the use of palmityl-oleyl-phosphatidylcholine (POPC) liposomes functionalized with ss-miR-216b conjugated with two palmityl chains and a lipid-modified cell penetrating peptide (TAT). These versatile nanoparticles suppressed oncogenic KRAS in PDAC cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas p21(ras) / Carcinoma Ductal Pancreático / MicroARNs / Proteínas Argonautas Límite: Humans Idioma: En Revista: RNA Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas p21(ras) / Carcinoma Ductal Pancreático / MicroARNs / Proteínas Argonautas Límite: Humans Idioma: En Revista: RNA Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos