Li Peixin, Yao Shengwen, Qi Wenqiang, Liu Hanwen, Zhang Xiaoyi, Zhou Bin, Zhang Shijie, Zhang Yaozhong, Liang Hao, Huang Huangwei, Zhao Yihao, Shi Benkang, Chen Jun, Liu Jingchao
Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Department of Urology, The Second Hospital of Shandong University, Jinan, Shandong, China.
J Cell Mol Med. 2025 Jul;29(14):e70710. doi: 10.1111/jcmm.70710.
Ferroptosis is an iron-dependent form of regulated cell death. Previous research indicates that inducing ferroptosis holds significant promise in cancer therapy, particularly for patients who have failed traditional treatments. However, the presence of a ferroptosis escape mechanism in bladder cancer remains unclear, and the therapeutic potential of ferroptosis induction in this context requires further exploration. In this study, bioinformatics analyses and immunohistochemical staining revealed that FADS2 is aberrantly overexpressed in bladder cancer, with its high expression correlating with poor prognosis. Both in vivo and in vitro experiments, including CCK-8 assays, lipid peroxidation assays, iron measurements and ferroptosis-related gene analyses, demonstrated that silencing FADS2 can trigger ferroptosis in bladder cancer cells. Mechanistically, inhibition of the mTOR pathway and SREBP activity was found to reduce FADS2 expression and promote ferroptosis in bladder cancer. In conclusion, this study identifies a critical gene involved in ferroptosis escape in bladder cancer and suggests that FADS2 could serve as a novel prognostic marker and therapeutic target.
铁死亡是一种铁依赖性的程序性细胞死亡形式。先前的研究表明，诱导铁死亡在癌症治疗中具有重大前景，尤其是对于那些传统治疗失败的患者。然而，膀胱癌中铁死亡逃逸机制的存在仍不清楚，在这种情况下诱导铁死亡的治疗潜力需要进一步探索。在本研究中，生物信息学分析和免疫组织化学染色显示，FADS2在膀胱癌中异常高表达，其高表达与不良预后相关。体内和体外实验，包括CCK-8测定、脂质过氧化测定、铁测量和铁死亡相关基因分析，均表明沉默FADS2可触发膀胱癌细胞的铁死亡。机制上，发现抑制mTOR通路和SREBP活性可降低FADS2表达并促进膀胱癌中的铁死亡。总之，本研究确定了一个参与膀胱癌铁死亡逃逸的关键基因，并表明FADS2可作为一种新的预后标志物和治疗靶点。
