Inhibition of miR-21 by 3'/5'-Serinyl-Capped 2'-O-Methyl RNA Interspersed With 2'-O-(2-Amino-3-Methoxypropyl) Uridine Units

Nucleic Acid Ther. 2016 Oct;26(5):327-334. doi: 10.1089/nat.2015.0591. Epub 2016 Jul 25.

Abstract

miRNAs are highly conserved class of small ncRNAs whose involvement in human pathophysiologies is extensively investigated. MiR-21 is a well established oncogenic miRNA whose deregulation plays a significant role in onset and progression of cancer. The need of novel approaches to downregulate miR-21 is rapidly expanding. Potent inhibition of miR-21 is achieved by chemically modified 2'-O-methyl RNA oligonucleotide. The serinol capping at 3' and 5'ends and the interspersed 2'-O-(R-2-amino-3-methoxypropyl) uridine units enhance the nuclease resistance and efficacy of 2'-O-methyl RNA for the inhibition of miR-21. This represents a simple and novel modification for developing oligonucleotide-based therapeutics.

Keywords: antagomirs; cancer; microRNA; noncoding RNA; oligonucleotides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antagomirs / chemical synthesis
  • Antagomirs / genetics*
  • Antagomirs / metabolism
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Base Sequence
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • MCF-7 Cells
  • Methylation
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Plasmids / chemistry
  • Plasmids / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Serine / chemistry*
  • Uridine / analogs & derivatives*

Substances

  • Antagomirs
  • Apoptosis Regulatory Proteins
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA-Binding Proteins
  • Serine
  • Luciferases
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Uridine