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Identifying circRNA-miRNA-mRNA Networks Associated with Osimertinib Resistance in Lung Adenocarcinoma by Analyzing

Fen Liu1, Xiyan Wang1, Wenjun Tian2

  • 1Department of Respiratory, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan, 250014, China.

Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer
|June 10, 2025
PubMed
Abstract

Insights

This study identified a circRNA-miRNA-mRNA network, specifically the hsa_circ_0078465/miR-183-5p/NRAS axis, which promotes osimertinib resistance in lung adenocarcinoma (LUAD). This finding offers potential therapeutic targets for overcoming drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Lung adenocarcinoma (LUAD) frequently develops resistance to osimertinib, a targeted therapy.
  • Understanding the molecular mechanisms underlying this resistance is crucial for improving patient outcomes.

Purpose of the Study:

  • To screen for circular RNAs (circRNAs) associated with osimertinib resistance in LUAD.
  • To construct a circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network.
  • To identify key molecular players in osimertinib resistance.

Main Methods:

  • Differential expression analysis using DESeq2 on GEO database data to identify circRNAs.
  • Intersection of differentially expressed miRNAs with circRNA targets and EGFR-related genes.
  • Validation of the identified hsa_circ_0078465/miR-183-5p/NRAS axis in cellular models.

Main Results:

  • A network linked osimertinib resistance-related circRNAs to six differentially expressed miRNAs and 35 EGFR-related mRNAs.
  • NRAS was identified as a hub gene within this network.
  • The hsa_circ_0078465/miR-183-5p/NRAS axis was validated and shown to promote proliferation and migration in osimertinib-resistant LUAD cells.

Conclusions:

  • The study proposes a novel circRNA-miRNA-mRNA network, specifically the hsa_circ_0078465/miR-183-5p/NRAS axis, implicated in osimertinib resistance in LUAD.
  • This axis plays a role in regulating cell motility and proliferation.
  • The findings provide potential therapeutic targets for overcoming osimertinib resistance in LUAD.

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