Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides

BMC Mol Biol. 2018 Jun 7;19(1):6. doi: 10.1186/s12867-018-0107-6.

Abstract

Background: Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recently, it has been demonstrated that gastric cancer cells display a specific miRNA expression profile, with increasing evidence of the role of miRNA-9 in this disease. miRNA-9 upregulation has been shown to influence the expression of E-cadherin-encoding gene, triggering cell motility and invasiveness.

Results: In this study, we designed LNA anti-miRNA oligonucleotides with a complementary sequence to miRNA-9 and tested their properties to both detect and silence the target miRNA. We could identify and visualize the in vitro uptake of low-dosing LNA-based anti-miRNA oligonucleotides without any carrier or transfection agent, as early as 2 h after the addition of the oligonucleotide sequence to the culture medium. Furthermore, we were able to assess the silencing potential of miRNA-9, using different LNA anti-miRNA oligonucleotide designs, and to observe its subsequent effect on E-cadherin expression.

Conclusions: The administration of anti-miRNA sequences even at low-doses, rapidly repressed the target miRNA, and influenced the expression of E-cadherin by significantly increasing its levels.

Keywords: E-cadherin; FISH; LNA-AMOs; Locked nucleic acid; MicroRNA; miR-9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • Oligonucleotides / pharmacology*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • MIRN92 microRNA, human
  • MicroRNAs
  • Oligonucleotides
  • locked nucleic acid