Preparation, characterization, and in vitro tumor-suppressive effect of anti-miR-21-equipped RNA nanoparticles

Biochem Biophys Res Commun. 2021 Jun 18:558:107-113. doi: 10.1016/j.bbrc.2021.04.040. Epub 2021 Apr 24.

Abstract

MicroRNAs play an irreplaceable role in gene expression regulation. Upregulation of several miRNAs increases the risk of invasion and metastasis of breast cancer cells. An oncogenic miRNA, miR-21, is highly expressed in triple-negative breast cancer (TNBC) and is associated with tumor proliferation, invasion, carcinogenesis, prognosis, and therapeutic resistance. However, targeted delivery of therapeutic anti-miRNAs into cancer cells remains challenging, especially for TNBC. In this study, we report the application of an RNA nanotechnology-based platform for the targeted delivery of anti-miR-21 by epidermal growth factor receptor (EGFR) aptamer in vitro to TNBC and chemical-resistant breast cancer cells. RNA nanoparticles reduced cell viability and sensitized breast cancer cells to doxorubicin (DOX) treatment in vitro. Inhibition of miR-21 by RNA nanoparticles suppressed TNBC cell invasion, migration, and colony formation. The results indicate the potential application of nanotechnology-based delivery platforms in clinical anti-cancer therapeutics.

Keywords: RNA nanoparticles; Triple-negative breast cancer; miR-21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Aptamers, Nucleotide / administration & dosage
  • Aptamers, Nucleotide / genetics*
  • Aptamers, Nucleotide / therapeutic use*
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Female
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics*
  • Molecular Targeted Therapy / methods
  • Nanoparticles / administration & dosage
  • Nanoparticles / therapeutic use
  • Nanotechnology
  • Neoplasm Invasiveness / genetics
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / therapy*
  • Tumor Stem Cell Assay

Substances

  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • MIRN21 microRNA, human
  • MicroRNAs
  • Doxorubicin
  • EGFR protein, human
  • ErbB Receptors