miR-365a-5p suppresses gefitinib resistance in non-small-cell lung cancer through targeting PELI3

Pharmacogenomics. 2020 Jul;21(11):771-783. doi: 10.2217/pgs-2020-0006. Epub 2020 Jul 8.

Abstract

Aim: Demonstrate the function of dysregulated miR-365a-5p-PELI3 signaling axis in the generation of gefitinib resistance during treatment for non-small-cell lung cancer (NSCLC). Patients & methods: All the NSCLC patients who participated in this research were recruited from the Second Hospital of Hebei Medical University. PC9 cells and PC9GR cells were cultured for in vitro experiments. Results: Patients who were primary resistant to EGFR-tyrosine kinase inhibitor had lower miR-365a-5p levels. MiR-365a-5p directly targeted PELI3 mRNA. MiR-365a-5p overexpression enhanced the function of gefitinib in inhibiting cell viability. Tumor growth was suppressed through miR-365a-5p in nude mice. Conclusion: Dysregulated miR-365a-5p-PELI3 signaling axis triggered the generation of gefitinib resistance in NSCLC.

Keywords: PELI3; gefitinib resistance; miR-365a-5p; non-small-cell lung cancer.

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gefitinib / pharmacology
  • Gefitinib / therapeutic use*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Ubiquitin-Protein Ligases / biosynthesis
  • Ubiquitin-Protein Ligases / genetics*
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • MIRN365 microRNA, human
  • MicroRNAs
  • PELI3 protein, human
  • Ubiquitin-Protein Ligases
  • Gefitinib