Related Experiment Video

Updated: Jun 9, 2026

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

Exosomal circ_0097112 drives icotinib resistance through activating RAF/MAPK signaling in lung adenocarcinoma

Ziyuan Chen1, Yu Wang2, Yier Xu2

  • 1Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315020, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China.

Cellular Signalling
|June 7, 2026
PubMed

Insights

Circular RNAs (circRNAs) like circ_0097112 are transferred via exosomes, driving drug resistance in lung adenocarcinoma (LUAD). Targeting this circRNA may reverse resistance to EGFR-TKI therapies.

Area of Science:

  • Molecular Oncology
  • Cancer Biology
  • RNA Biology

Background:

  • Exosomes mediate therapeutic resistance by transferring bioactive molecules, including circular RNAs (circRNAs).
  • Lung adenocarcinoma (LUAD) often develops resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs).
  • circRNAs are implicated as key players in cancer progression and drug resistance.

Purpose of the Study:

  • To identify and characterize the role of specific circRNAs in EGFR-TKI resistance in LUAD.
  • To elucidate the molecular mechanism by which circ_0097112 contributes to acquired drug resistance.
  • To explore circ_0097112 as a potential therapeutic target for overcoming EGFR-TKI resistance.

Main Methods:

  • Bioinformatic analysis of public databases to identify candidate circRNAs.
  • In vitro experiments using LUAD cell lines to assess the functional role of circ_0097112.
  • Confocal microscopy to visualize exosome-mediated cargo transfer.
  • RNA pull-down and RNA immunoprecipitation assays to determine molecular interactions.

Main Results:

  • circ_0097112 was significantly upregulated in EGFR-TKI-resistant LUAD cells and their secreted exosomes.
  • circ_0097112 promoted LUAD cell proliferation and inhibited apoptosis.
  • Resistant cells transferred circ_0097112 via exosomes to sensitive cells, conferring acquired resistance.
  • circ_0097112 directly interacted with UPF1, stabilizing oncogenic NRAS mRNA and activating the RAF/MAPK pathway.

Conclusions:

  • The circ_0097112/UPF1/NRAS axis is a critical driver of EGFR-TKI resistance in LUAD.
  • Exosome-mediated transfer of circ_0097112 plays a key role in conferring acquired drug resistance.
  • Targeting circ_0097112 presents a novel therapeutic strategy to overcome EGFR-TKI resistance in lung cancer.
Keywords:
Circular RNAEGFR-TKI resistanceExosomesNon-small-cell lung cancer

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