膀胱癌（BC）是男性泌尿系统最常见的恶性肿瘤之一，目前缺乏最佳的治疗策略。为了从环状RNA的角度阐明BC的致病机制，我们进行了本研究。基于我们之前的研究，一种新型的 circRNA circPKN2 引起了我们的兴趣，因为它在 BC 中显着下调，并且与 BC 患者的预后密切相关。我们的研究结果表明，circPKN2可以在体外抑制BC细胞的增殖和迁移。此外，我们发现circPKN2通过促进铁死亡在BC中发挥抗癌作用。机制研究表明，circPKN2 招募 STUB1 来促进 SCD1 泛素化，从而抑制 WNT 通路并促进 BC 中的铁死亡。此外，我们的研究揭示了剪接因子 QKI 在 circPKN2 生物发生中的调节作用。动物研究表明，circPKN2 可增强体内 BC 细胞的铁死亡，抑制肿瘤生长和转移。抗癌因子 circPKN2 的发现有望为 BC 的预防和治疗提供新的治疗靶点。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

Bladder cancer (BC) is one of the most common malignancies in the male urinary system and currently lacks an optimal treatment strategy. To elucidate the pathogenic mechanisms of BC from the perspective of circular RNAs, we conducted this study. Building upon our previous research, a novel circRNA, circPKN2, captured our interest due to its significant downregulation in BC, and its close association with the prognosis of BC patients. Our research findings indicate that circPKN2 can inhibit the proliferation and migration of BC cells in vitro. Furthermore, we discovered that circPKN2 exerts its anti-cancer effects in BC by promoting ferroptosis. Mechanistic studies revealed that circPKN2 recruits STUB1 to facilitate the ubiquitination of SCD1, thereby suppressing the WNT pathway and promoting ferroptosis in BC. Additionally, our research unveiled the regulatory role of the splicing factor QKI in the biogenesis of circPKN2. Animal studies demonstrated that circPKN2 enhances ferroptosis in BC cells in vivo, inhibiting tumor growth and metastasis. The discovery of the anti-cancer factor circPKN2 holds promise for providing new therapeutic targets in the prevention and treatment of BC.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.