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Aptamer-miR-34c Conjugate Affects Cell Proliferation of Non-Small-Cell Lung Cancer Cells

Valentina Russo1, Alessia Paciocco1, Alessandra Affinito1

  • 1Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.

Molecular Therapy. Nucleic Acids
|October 20, 2018
PubMed

Insights

Restoring oncosuppressor miR-34c-3p in non-small-cell lung carcinoma (NSCLC) inhibits cancer cell survival. A novel chimera delivers miR-34c-3p to AXL-expressing NSCLC cells, overcoming drug resistance.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biotechnology

Background:

  • MicroRNAs (miRNAs) are crucial regulators of cellular processes and emerging cancer therapeutics.
  • Downregulation of the oncosuppressor miR-34c-3p is observed in non-small-cell lung carcinoma (NSCLC).
  • AXL receptor is implicated in NSCLC malignancy and acquired resistance to receptor tyrosine kinase (RTK) inhibitors.

Purpose of the Study:

  • To investigate the therapeutic potential of reintroducing miR-34c-3p in NSCLC.
  • To develop a targeted delivery system for miR-34c-3p using the AXL-targeting aptamer GL21.T.
  • To evaluate the efficacy of the GL21.T/miR-34c chimera in NSCLC treatment.

Main Methods:

  • In vitro studies assessing NSCLC cell survival and proliferation.
  • Conjugation of miR-34c-3p to the GL21.T aptamer for targeted delivery.
  • Evaluation of the chimera's ability to overcome acquired RTK-inhibitor resistance.

Main Results:

  • Reintroduction of miR-34c-3p reduced NSCLC cell survival in vitro.
  • The GL21.T/miR-34c chimera selectively targeted AXL-expressing NSCLC cells.
  • The chimera demonstrated efficacy in overcoming acquired RTK-inhibitor resistance.
  • Dual inhibition of AXL at functional and transcriptional levels was observed.

Conclusions:

  • The GL21.T/miR-34c chimera is a promising therapeutic tool for NSCLC.
  • Targeted delivery of miR-34c-3p can overcome drug resistance in NSCLC.
  • This dual-action chimera offers a novel strategy for NSCLC treatment.
Keywords:
NSCLCaptamerlung cancermiRNAtherapeutics

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