铜中毒是由铜离子引起的细胞死亡过程，由与硫辛酸代谢相关的蛋白质脂化介导。铜凋亡与多种肿瘤的进展及预后密切相关。在这里，我们发现硫辛酸转移酶 1 (LIPT1) 是与铜凋亡相关的关键基因，在膀胱癌 (BLCA) 中表达下调，并且与患者不良预后相关。恢复 BLCA 细胞中 LIPT1 的表达可抑制增殖并促进铜凋亡。此外，RNA测序和Bodipy染色的结果表明，LIPT1介导的代谢途径抑制细胞内脂滴的积累，破坏内质网（ER）稳态，促进细胞凋亡。此外，LIPT1的过度表达不仅在体外而且在体内抑制BLCA细胞的增殖率。从机制上讲，YTH N6-甲基腺苷 RNA 结合蛋白 F2 (YTHDF2) 以 m6A 依赖性方式促进 LIPT1 mRNA 的降解。综上所述，这些结论揭示了LIPT1通过促进铜中毒和内质网应激来抑制BLCA的进展，表明LIPT1将为治疗BLCA提供强有力的治疗方向和药物靶点。© 2024。作者，获得Springer独家许可自然有限公司。

Cuproptosis, a cell death process caused by copper ions, is mediated by protein lipidation related to lipoic acid metabolism. There is a close connection between cuproptosis and the progression and prognosis of various tumors. Here, we identified lipoyltransferase 1 (LIPT1), a key gene related to cuproptosis, was downregulated in bladder cancer (BLCA) and was associated with unfavorable patient prognosis. Restoring the LIPT1 expression in BLCA cells suppressed the proliferation and promoted cuproptosis. Moreover, the consequences of RNA sequencing and Bodipy staining showed that the metabolic pathway mediated by LIPT1 inhibited the accumulation of lipid droplets in cells, disrupted endoplasmic reticulum (ER) homeostasis, and promoted cell apoptosis. Additionally, overexpression of LIPT1 not only repressed the proliferation rate of BLCA cells in vitro but also in vivo. Mechanistically, YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) promoted the degradation of LIPT1 mRNA in a m6A-dependent manner. In summary, these conclusions reveal that LIPT1 promotes cuprotosis and ER stress to inhibit the progression of BLCA, indicating that LIPT1 will provide a powerful treatment direction and drug target for treating BLCA.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.