title: Peptide nucleic acids targeting miR-221 modulate p27Kip1 expression             in breast cancer MDA-MB-231 cells.
abstract: The activity of a peptide nucleic acid (PNA) targeting cancer-associated             microRNA-221 is described. PNAs against miR-221 were designed in order to bind             very efficiently to the target RNA strand and to undergo efficient uptake in the             cells. A polyarginine-PNA conjugate targeted against miR-221 (Rpep-PNA-a221) showed             both very high affinity for RNA and efficient cellular uptake without the addition             of transfection reagents. Unmodified PNA with the same sequence displayed RNA             binding, but cellular uptake was very poor. Consistently, only Rpep-PNA-a221 strongly             inhibited miR-221. Targeting miR-221 by PNA resulted in i) lowering of the hybridization             levels of miR-221 measured by RT-qPCR, ii) upregulation of p27Kip1 gene expression,             measured by RT-qPCR and western blot analysis. The major conclusion of this study             is that efficient delivery of anti‑miR PNA through a suitable peptide carrier             (Rpep‑PNA-a221) leads to inhibition of miR-221 activity, altering the expression             of miR-221-regulated functions in breast cancer cells.
authors.affiliation: BioPharmaNet, Department of Biochemistry and Molecular Biology,                     Ferrara University, Ferrara, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brognara
authors.forename: Enrica
authors.initials: E
authors.lastname: Fabbri
authors.forename: Fabio
authors.initials: F
authors.lastname: Aimi
authors.forename: Alex
authors.initials: A
authors.lastname: Manicardi
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.forename: Alessia
authors.initials: A
authors.lastname: Finotti
authors.forename: Giulia
authors.initials: G
authors.lastname: Breveglieri
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Roberto
authors.initials: R
authors.lastname: Corradini
authors.forename: Rosangela
authors.initials: R
authors.lastname: Marchelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D023061:Gene Order; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D035683:MicroRNAs; D020135:Peptide Nucleic Acids; C525709:MIR221, human