膀胱癌（BC）是一种普遍且可怕的恶性肿瘤，需要创新的诊断和治疗策略。环状 RNA (circRNA) 已成为癌症生物学中的重要调节因子。在这项研究中，我们利用脂质过氧化评估、透射电子显微镜和丙二醛 (MDA) 测量等技术全面评估了 BC 细胞的铁死亡水平。此外，我们采用 RNA Pull-down、RNA 免疫沉淀 (RIP) 和免疫沉淀 (IP) 测定法探讨了 circRNA 控制 BC 的复杂机制。我们的调查揭示了 circSIRT5，它在 BC 地区显示出显着的下调。值得注意的是，circSIRT5 成为一种有前途的预后标志物，其表达减少与不利的临床结果相关。从功能上讲，circSIRT5 在体外和体内均被鉴定为 BC 进展的抑制剂。从机制上讲，circSIRT5通过形成涉及circSIRT5、SYVN1和PHGDH的三元复合物来发挥其肿瘤抑制活性。该复合物增强了 PHGDH 的泛素化和随后的降解，最终促进 BC 细胞中的铁死亡。这种铁死亡过程对抑制 BC 中的肿瘤生长和转移有显着贡献。此外，FUS 被发现可以加速 BC 中 circSIRT5 的生物合成。这些发现为 circSIRT5 在 BC 发病机制中的关键作用提供了有价值的见解，强调了其作为这种恶性肿瘤的诊断生物标志物和治疗靶点的潜力。© 2024。作者。

Bladder cancer (BC) represents a prevalent and formidable malignancy necessitating innovative diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have emerged as crucial regulators in cancer biology. In this study, we comprehensively evaluated ferroptosis levels in BC cells utilizing techniques encompassing lipid peroxidation assessment, transmission electron microscopy, and malondialdehyde (MDA) measurement. Additionally, we probed into the mechanistic intricacies by which circRNAs govern BC, employing RNA pull-down, RNA immunoprecipitation (RIP), and immunoprecipitation (IP) assays. Our investigation unveiled circSIRT5, which displayed significant downregulation in BC. Notably, circSIRT5 emerged as a promising prognostic marker, with diminished expression correlating with unfavorable clinical outcomes. Functionally, circSIRT5 was identified as an inhibitor of BC progression both in vitro and in vivo. Mechanistically, circSIRT5 exerted its tumor-suppressive activities through the formation of a ternary complex involving circSIRT5, SYVN1, and PHGDH. This complex enhanced the ubiquitination and subsequent degradation of PHGDH, ultimately promoting ferroptosis in BC cells. This ferroptotic process contributed significantly to the inhibition of tumor growth and metastasis in BC. In addition, FUS was found to accelerate the biogenesis of circSIRT5 in BC. These findings provide valuable insights into the pivotal role of circSIRT5 in BC pathogenesis, underscoring its potential as a diagnostic biomarker and therapeutic target for this malignancy.© 2024. The Author(s).