title: Molecular methods for validation of the biological activity of peptide nucleic acids targeting microRNAs.
abstract: The involvement of microRNAs in human pathologies is a firmly established fact. Accordingly, the pharmacological modulation of their activity appears to be a very appealing issue in the development of new types of drugs (miRNA therapeutics). One of the most interesting issues is the possible development of miRNA therapeutics for development of anti-cancer molecules. In this respect appealing molecules are based on peptide nucleic acids (PNAs), displaying a pseudo-peptide backbone composed of N-(2-aminoethyl)glycine units and found to be excellent candidates for antisense and antigene therapies. The major limit in the use of PNAs for alteration of gene expression is the low uptake by eukaryotic cells. The aim of this chapter is to describe methods for determining the activity of PNAs designed to target oncomiRNAs, using as model system miR-221 and its target p27(Kip1) mRNA. The effects of PNAs targeting miR-221 are here presented discussing data obtained using as model system the human breast cancer cell line MDA-MB-231, in which miR-221 is up-regulated and p27(Kip1) down-regulated.
authors.affiliation: Department of Life Sciences and Biotechnology, Ferrara University, Ferrara, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brognara
authors.forename: Enrica
authors.initials: E
authors.lastname: Fabbri
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.forename: Alessia
authors.initials: A
authors.lastname: Finotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Corradini
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs; D020135:Peptide Nucleic Acids; C525709:MIR221, human