Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 16, Pages -Publisher
MDPI
DOI: 10.3390/ijms23169348
Keywords
peptide nucleic acids; cystic fibrosis; microRNAs; miRNA targeting; miR-101-3p; miR-145-5p; CFTR
Funding
- Fondazione Fibrosi Cistica (FFC) [7/2018]
- Italian Ministry for Education, University and Research (MIUR)
- FAR (University Fund for Scientific Research, FAR-AF-Unife-2018)
- FAR (University Fund for Scientific Research, FAR-AF-Unife-2019)
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The study found that targeting CFTR-regulating microRNAs with antisense PNAs can increase CFTR production. Particularly, highly effective combinations were identified with PNAs targeting miR-145-5p and miR-101-3p in the treatment of Calu-3 cells.
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene encodes for a chloride channel defective in Cystic Fibrosis (CF). Accordingly, upregulation of its expression might be relevant for the development of therapeutic protocols for CF. MicroRNAs are deeply involved in the CFTR regulation and their targeting with miRNA inhibitors (including those based on Peptide Nucleic Acids, PNAs)is associated with CFTR upregulation. Targeting of miR-145-5p, miR-101-3p, and miR-335-5p with antisense PNAs was found to be associated with CFTR upregulation. The main objective of this study was to verify whether combined treatments with the most active PNAs are associated with increased CFTR gene expression. The data obtained demonstrate that synergism of upregulation of CFTR production can be obtained by combined treatments of Calu-3 cells with antisense PNAs targeting CFTR-regulating microRNAs. In particular, highly effective combinations were found with PNAs targeting miR-145-5p and miR-101-3p. Content of mRNAs was analyzed by RT-qPCR, the CFTR production by Western blotting. Combined treatment with antagomiRNAs might lead to maximized upregulation of CFTR and should be considered in the development of protocols for CFTR activation in pathological conditions in which CFTR gene expression is lacking, such as Cystic Fibrosis.
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