%0 Journal Article %A Ferino, Annalisa %A Miglietta, Giulia %A Picco, Raffaella %A Vogel, Stefan %A Wengel, Jesper %A Xodo, Luigi E. %D 2018 %T MicroRNA therapeutics: design of single-stranded miR-216b mimics to target KRAS in pancreatic cancer cells %U https://tandf.figshare.com/articles/journal_contribution/MicroRNA_therapeutics_design_of_single-stranded_miR-216b_mimics_to_target_i_KRAS_i_in_pancreatic_cancer_cells/7195109 %R 10.6084/m9.figshare.7195109.v1 %2 https://tandf.figshare.com/ndownloader/files/13247345 %K KRAS %K PDAC cells %K miR-216b %K AGO2 %K POPC liposome %X

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 5สน 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.

%I Taylor & Francis