Tumor-derived exosomal circRNA_102481 contributes to EGFR-TKIs resistance via the miR-30a-5p/ROR1 axis in non-small

Bo Yang1, Fei Teng2, Liang Chang1

  • 1Department of Thoracic Surgery, The First Hospital of Jilin University, Chaoyang, Changchun, Jilin, China.

Aging
|May 6, 2021
PubMed

Insights

Circular RNA (circRNA) in exosomes promotes non-small cell lung cancer (NSCLC) resistance to EGFR-TKIs. This exosomal circRNA_102481 may be a diagnostic biomarker and therapeutic target for NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Exosomes mediate intercellular communication and signal transduction.
  • Aberrant circular RNA (circRNA) expression is implicated in tumor development.
  • Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) are crucial in non-small cell lung cancer (NSCLC) treatment, but resistance remains a challenge.

Purpose of the Study:

  • To investigate the role of exosomal circRNAs in EGFR-TKI resistance in NSCLC.
  • To identify specific circRNAs involved in this resistance mechanism.
  • To elucidate the molecular pathways through which exosomal circRNAs mediate resistance.

Main Methods:

  • Serum exosomes were isolated from NSCLC patients before and after developing EGFR-TKI resistance.
  • circRNA expression profiling was performed using a circRNA microarray.
  • Functional assays (cell proliferation, apoptosis) and molecular mechanism studies (RNA pull-down, dual-luciferase reporter assays) were conducted.

Main Results:

  • Exosomes containing circRNA_102481 were significantly upregulated in EGFR-TKI resistant NSCLC.
  • circRNA_102481 secreted by resistant cells via exosomes inhibited proliferation and promoted apoptosis in resistant cells, while promoting proliferation and inhibiting apoptosis in sensitive cells.
  • circRNA_102481 acted as a sponge for miR-30a-5p, regulating ROR1 expression.

Conclusions:

  • Tumor-derived exosomal circRNA_102481 contributes to EGFR-TKI resistance in NSCLC through the miR-30a-5p/ROR1 axis.
  • Exosomal circRNA_102481 is associated with clinical parameters including TNM stage, differentiation, metastasis, and patient survival.
  • Exosomal circRNA_102481 presents a potential novel diagnostic biomarker and therapeutic target for EGFR-TKI resistance in NSCLC.

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