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

作者：Zihao Kong, Min Zhang, Hui Yuan, J. B. Liu, Huaiming Sang, Ping Zhao, Miao Xu, Chuanlong Zhu, Guoxin Zhang · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-08441-w · 被引用次数：10 · 研究领域：MicroRNA in disease regulation、Ferroptosis and cancer prognosis、Circular RNAs in diseases

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.