Exploitation of a very small peptide nucleic acid as a new inhibitor of miR-509-3p involved in the regulation of cystic fibrosis disease-gene expression.
Computational techniques, and in particular molecular dynamics (MD) simulations, have been successfully used as a complementary technique to predict and analyse the structural behaviour of nucleic acids, including peptide nucleic acid- (PNA-) RNA hybrids. This study shows that a 7-base long PNA complementary to the seed region of miR-509-3p, one of the miRNAs involved in the posttranscriptional regulation of the CFTR disease-gene of Cystic Fibrosis, and bearing suitable functionalization at its N- and C-ends aimed at improving its resistance to nucleases and cellular uptake, is able to revert the expression of the luciferase gene containing the 3'UTR of the gene in A549 human lung cancer cells, in agreement with the MD results that pointed at the formation of a stable RNA/PNA heteroduplex notwithstanding the short sequence of the latter. The here reported results widen the interest towards the use of small PNAs as effective anti-miRNA agents.
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Via Pansini 5, 80131 Napoli, Italy ; CEINGE-Biotecnologie Avanzate, 80131 Napoli, Italy.
Felice
0000-0002-0596-2933
F
Amato
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Via Pansini 5, 80131 Napoli, Italy ; CEINGE-Biotecnologie Avanzate, 80131 Napoli, Italy.
Rossella
R
Tomaiuolo
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Fabrizia
F
Nici
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Nicola
N
Borbone
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Via Pansini 5, 80131 Napoli, Italy ; CEINGE-Biotecnologie Avanzate, 80131 Napoli, Italy ; Università Telematica Pegaso, 80143 Napoli, Italy.
Ausilia
A
Elce
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Bruno
B
Catalanotti
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Stefano
S
D'Errico
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Carmine Marco
0000-0002-6164-7647
CM
Morgillo
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Giuseppe
0000-0002-1210-1269
G
De Rosa
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Laura
L
Mayol
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Gennaro
0000-0002-1313-2091
G
Piccialli
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Giorgia
G
Oliviero
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Via Pansini 5, 80131 Napoli, Italy ; CEINGE-Biotecnologie Avanzate, 80131 Napoli, Italy.
Giuseppe
0000-0002-4036-0874
G
Castaldo
D045744:Cell Line, Tumor; D002942:Circular Dichroism; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009691:Nucleic Acid Denaturation / Q000187:drug effects / Q000528:radiation effects; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use*; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
C571982:MIRN509 microRNA, human; D035683:MicroRNAs; D020135:Peptide Nucleic Acids; D016650:Fluorescein-5-isothiocyanate