Volume 7 Issue 2
A Peptide Nucleic Acid against MicroRNA miR-145-5p Enhances the Expression of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Calu-3 Cells
Enrica Fabbri, Anna Tamanini, Tiziana Jakova, Jessica Gasparello, Alex Manicardi, Roberto Corradini, Giuseppe Sabbioni, Alessia Finotti, Monica Borgatti, Ilaria Lampronti, Silvia Munari, Maria Cristina Dechecchi, Giulio Cabrini and Roberto Gambari
1Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy
2Laboratory of Molecular Pathology, University-Hospital, 37126 Verona, Italy
3Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy
*Author to whom correspondence should be addressed.
†Current address: Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 S4 B-9000 Gent, Belgium.
Abstract
Peptide nucleic acids (PNAs) are very useful tools for gene regulation at different levels, but in particular in the last years their use for targeting microRNA (anti-miR PNAs) has provided impressive advancements. In this respect, microRNAs related to the repression of cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is defective in cystic fibrosis, are of great importance in the development of new type of treatments. In this paper we propose the use of an anti-miR PNA for targeting miR-145, a microRNA reported to suppress CFTR expression. Octaarginine-anti-miR PNA conjugates were delivered to Calu-3 cells, exerting sequence dependent targeting of miR-145-5p. This allowed to enhance expression of the miR-145 regulated CFTR gene, analyzed at mRNA (RT-qPCR, Reverse Transcription quantitative Polymerase Chain Reaction) and CFTR protein (Western blotting) level.
Keywords:peptide nucleic acids; cystic fibrosis; microRNAs; miR-145; miRNA targeting; delivery; CFTR