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MiR-182 enhances radioresistance in non-small cell lung cancer cells by regulating FOXO3

Gang Chen1, Lina Yu1, Hui Dong1

  • 1Department of Respiratory Medicine, People's Hospital of Haining, Haining, China.

Clinical and Experimental Pharmacology & Physiology
|October 12, 2018
PubMed

Insights

MicroRNA-182 (miRNA-182) promotes lung cancer radioresistance by inhibiting FOXO3. Inhibiting miRNA-182 enhances radiation sensitivity, offering a new target for lung cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy

Background:

  • MicroRNA-182 (miRNA-182) is upregulated in lung cancer and linked to proliferation and chemoresistance.
  • The role of miRNA-182 in radioresistance, a key challenge in radiotherapy, remains largely unexplored.

Purpose of the Study:

  • To investigate the effect of miRNA-182 inhibition on lung cancer cell sensitivity to ionizing radiation.
  • To elucidate the underlying molecular mechanisms of miRNA-182 in radioresistance.

Main Methods:

  • Quantitative real-time PCR to assess miRNA-182 levels in lung cancer tissues and cell lines.
  • MiRNA-182 knockdown using small interfering RNAs (siRNAs).
  • Cell proliferation assays, apoptosis assays, and cell cycle analysis post-irradiation.
  • Western blotting to detect protein expression, including FOXO3.
  • Luciferase reporter assays to confirm direct targeting of FOXO3 by miRNA-182.

Main Results:

  • MiRNA-182 is confirmed to be upregulated in lung cancer tissues and responsive to irradiation.
  • MiRNA-182 knockdown significantly suppressed cell proliferation and increased apoptosis following irradiation.
  • Cells with reduced miRNA-182 exhibited unrepaired DNA damage, leading to cell cycle arrest.
  • FOXO3 was identified as a direct target of miRNA-182, and its overexpression reversed the radiosensitizing effect of miRNA-182 knockdown.

Conclusions:

  • MiRNA-182 plays a crucial role in conferring radioresistance in lung cancer.
  • The miRNA-182-FOXO3 axis represents a novel therapeutic target for overcoming radioresistance in lung cancer patients.
Keywords:
FOXO3lung cancermiR-182radiotherapy

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