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

Biomed Res Int. 2014;2014:610718. doi: 10.1155/2014/610718. Epub 2014 Apr 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Circular Dichroism
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / genetics*
  • Electrophoretic Mobility Shift Assay
  • Fluorescein-5-isothiocyanate / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Molecular Dynamics Simulation
  • Nucleic Acid Denaturation / drug effects
  • Nucleic Acid Denaturation / radiation effects
  • Peptide Nucleic Acids / chemical synthesis
  • Peptide Nucleic Acids / pharmacology*
  • Peptide Nucleic Acids / therapeutic use*
  • Spectrophotometry, Ultraviolet
  • Ultraviolet Rays

Substances

  • MIRN509 microRNA, human
  • MicroRNAs
  • Peptide Nucleic Acids
  • Fluorescein-5-isothiocyanate