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Regulating Oncogenic LncRNA DANCR with Targeted ECO/siRNA Nanoparticles for Non-Small Cell Lung Cancer Therapy

Calin Nicolescu1, Amita Vaidya1, Andrew Schilb1

  • 1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States.

ACS Omega
|July 11, 2022
PubMed

Insights

Targeting the long noncoding RNA DANCR with nanoparticles effectively silenced it in non-small cell lung cancer cells. This approach inhibited cancer cell migration and invasion, offering a potential therapy for NSCLC.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Nanotechnology

Background:

  • Long noncoding RNA (lncRNA) differentiation antagonizing noncoding RNA (DANCR) is an oncogenic factor overexpressed in non-small cell lung cancer (NSCLC).
  • DANCR influences cancer cell migration and invasion, making it a potential therapeutic target.
  • NSCLC is the most common lung cancer subtype with a high mortality rate.

Purpose of the Study:

  • To investigate the efficacy of nanoparticle-mediated delivery of small interfering RNA against DANCR (siDANCR) for NSCLC treatment.
  • To evaluate the impact of DANCR knockdown on NSCLC cell migration, invasion, and spheroid formation.
  • To assess the potential of DANCR targeting in overcoming resistance to epidermal growth factor receptor (EGFR) inhibitors.

Main Methods:

  • Utilized arginine-glycine-aspartic acid (RGD)-poly(ethylene glycol) (PEG)-(1-aminoethyl)-iminobis[N-oleicylcysteinyl-1-aminoethyl)propionamide] (ECO)/siDANCR nanoparticles for transfection in A549 and NCI-H1299 NSCLC cell lines.
  • Quantified DANCR silencing efficiency and assessed its effects on cell migration, invasion, and spheroid formation.
  • Evaluated the impact of DANCR knockdown on EGFR-inhibitor resistant NSCLC cells and their response to EGFR inhibitors.

Main Results:

  • Achieved over 90% DANCR silencing using RGD-PEG-ECO/siDANCR nanoparticles.
  • Observed significant inhibition of cell migration, invasion, and spheroid formation compared to control siRNA.
  • Demonstrated reduced migration and invasion in EGFR-inhibitor resistant NSCLC cells, with resensitization to EGFR inhibitors.
  • Sustained DANCR silencing for up to 7 days post-single transfection.

Conclusions:

  • Nanoparticle-mediated RNA interference targeting DANCR is a promising therapeutic strategy for NSCLC.
  • This approach effectively regulates cancer cell migration and invasion.
  • It holds potential for improving treatment response in EGFR-inhibitor resistant NSCLC.

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