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An Orthotopic Bladder Cancer Model for Gene Delivery Studies
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CircZNF609 inhibited bladder cancer immunotherapy sensitivity via enhancing fatty acid uptake through IGF2BP2/CD36

Kai Li1, Jiancheng Lv2, Jun Wang3

  • 1Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

International Immunopharmacology
|June 15, 2024
PubMed

Insights

Circular RNAs (circRNAs) promote bladder cancer immune escape and reduce immunotherapy effectiveness. CircZNF609, via the IGF2BP2/CD36 pathway, enhances tumor immune evasion, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Circular RNAs (circRNAs) are implicated in immune regulation.
  • CircZNF609 is an oncogene previously linked to reduced chemosensitivity in bladder cancer (BCa).
  • The role of circZNF609 in BCa immune escape and immunotherapy response is unexplored.

Purpose of the Study:

  • To investigate the function of circZNF609 in bladder cancer immune escape.
  • To determine the impact of circZNF609 on BCa sensitivity to immunotherapy.
  • To elucidate the molecular mechanisms underlying circZNF609's effects.

Main Methods:

  • Co-culture assays of BCa cells and CD8+ T cells.
  • In vivo studies using cell line-derived and patient-derived xenograft mouse models with human immune reconstitution.
  • Analysis of the circZNF609/IGF2BP2/CD36 signaling pathway.

Main Results:

  • Overexpression of circZNF609 enhanced BCa immune escape both in vitro and in vivo.
  • CircZNF609 binds to IGF2BP2, stabilizing CD36 mRNA and increasing fatty acid uptake by BCa cells.
  • DDX39B regulates the nuclear export of circZNF609, contributing to the pathway.

Conclusions:

  • CircZNF609 promotes bladder cancer immune escape and suppresses immunotherapy sensitivity through the novel circZNF609/IGF2BP2/CD36 cascade.
  • CircZNF609 represents a potential biomarker and therapeutic target for bladder cancer immunotherapy.
Keywords:
Bladder cancerCD36Circular RNAIGF2BP2Immunotherapy

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