缺氧在胰腺导管腺癌（PDAC）化疗耐药中的机制仍不清楚。在这项研究中，我们揭示了 miR-485-3p 在 PDAC 中的重要作用，特别是它在缺氧条件下对癌症干性和吉西他滨耐药性的影响。我们发现 PDAC 组织中 miR-485-3p 大幅下调，表达较低与患者预后不良相关。从机制上讲，miR-485-3p影响干性特征，过表达时肿瘤球形成减少和对吉西他滨敏感性增加就证明了这一点。此外，我们确定 SOX9 和 SLC7A11 是 miR-485-3p 的两个靶标，它们在干细胞性和铁死亡中发挥着至关重要的作用。缺氧条件下，DNMT3B表达上调，导致miR-485-3p启动子区域高甲基化。 miR-485-3p 表达的减少促进了 PDAC 的干性和化疗耐药性。总之，我们的研究结果阐明了 PDAC 中缺氧、表观遗传修饰和铁死亡之间错综复杂的相互作用，并揭示了调节癌症干性和化疗敏感性的靶向干预措施的潜在途径，为改进 PDAC 治疗策略提供了前景。© 2024。作者（ s）。

The mechanism of hypoxia in chemoresistance of pancreatic ductal adenocarcinoma (PDAC) remains elusive. In this study, we revealed the essential role of miR-485-3p in PDAC, particularly its impact on cancer stemness and gemcitabine resistance under hypoxic conditions. We found substantial downregulation of miR-485-3p in PDAC tissues, with lower expression correlating to poor patient outcomes. Mechanistically, miR-485-3p influenced stemness characteristics, as evidenced by reduced tumor-sphere formation and increased sensitivity to gemcitabine upon overexpression. Moreover, we identified SOX9 and SLC7A11 as two targets of miR-485-3p, which play a vital role in stemness and ferroptosis. Under the hypoxic condition, DNMT3B expression was upregulated, leading to hypermethylation of the miR-485-3p promoter region. The reduced miR-485-3p expression promoted stemness and chemoresistance of PDAC. In conclusion, our findings elucidate the intricate interplay of hypoxia, epigenetic modifications, and ferroptosis in PDAC and shed light on potential avenues for targeted interventions that modulate cancer stemness and chemosensitivity, offering prospects for improved therapeutic strategies for PDAC.© 2024. The Author(s).