Exo-miR-1911-5p regulates ferroptosis to promote macrophages M2 polarization-mediated gastric cancer cisplatin resistance via MYB/AKR1B10/ACC

  • Commun Biol. 2025 Jul 15;8(1):1054. doi: 10.1038/s42003-025-08441-w.
Zihao Kong  #  1  2 ,  Min Zhang  #  3 ,  Hui Yuan  #  4 ,  Jiahao Liu  #  1 ,  Huaiming Sang  1 ,  Ping Zhao  1 ,  Miao Xu  1 ,  Chuanlong Zhu  5 ,  Guoxin Zhang  6
Affiliations
  • 1. Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 2. Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  • 3. Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou, China.
  • 4. Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 5. Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. [email protected].
  • 6. Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. [email protected].
  • # Contributed equally.
PMID: 40664751 DOI: 10.1038/s42003-025-08441-w
Abstract

Tumor-associated macrophages (TAMs) have been implicated in fostering various hallmarks of Cancer progression in gastric Cancer (GC). However, the intricate molecular mechanisms underlying TAM-induced chemoresistance remain incompletely understood. Exosomes emerge as key players, mediating TAM-induced resistance to cisplatin (DDP) by regulating Ferroptosis. Our investigation reveals that exo-miR-1911-5p, delivered to GC cells from TAMs, significantly contributes to cisplatin resistance. Specifically, direct modulation of MYB by MiR-1911-5p leads to decreased expression of AKR1B10, a crucial factor in preventing Ferroptosis. Further exploration confirms the regulation of ACC by AKR1B10. Through targeting the MYB/AKR1B10/ACC axis, exo-miR-1911-5p inhibits Ferroptosis to enhances cisplatin resistance. Additionally, exo-miR-1911-5p promotes M2 polarization of TAMs by targeting ARHGEF3. Collectively, our findings highlight the critical role of exo-miR-1911-5p in mediating cisplatin resistance through modulating the cross-talk between TAMs and GC. Targeting exo-miR-1911-5p could represent a promising strategy for overcoming DDP resistance in GC.

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