10.6084/m9.figshare.7195109.v1
Annalisa Ferino
Annalisa
Ferino
Giulia Miglietta
Giulia
Miglietta
Raffaella Picco
Raffaella
Picco
Stefan Vogel
Stefan
Vogel
Jesper Wengel
Jesper
Wengel
Luigi E. Xodo
Luigi E.
Xodo
MicroRNA therapeutics: design of single-stranded miR-216b mimics to target <i>KRAS</i> in pancreatic cancer cells
Taylor & Francis Group
2018
KRAS
PDAC cells
miR-216b
AGO2
POPC liposome
2018-10-11 09:44:31
Journal contribution
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
<p>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 <i>KRAS</i>, whose mutant G12D allele drives the pathogenesis of PDAC, is a target of miR-216b. To suppress oncogenic <i>KRAS</i> 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 <i>KRAS</i> 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 <i>KRAS</i>. 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 <i>KRAS</i> in PDAC cells.</p>