与 DNA 基因融合不同，嵌合 RNA 已成为在癌症治疗中具有多种功能的有前景的治疗靶点。然而，大多数嵌合RNA的功能意义和治疗潜力仍不清楚。在这里，我们鉴定了溶质载体家族 2-成员 11 (SLC2A11) 和巨噬细胞迁移抑制因子 (MIF) 的新型融合转录本。在这项研究中，我们调查了癌症基因组图谱队列和孙逸仙纪念医院患者队列中 SLC2A11-MIF 的上调情况。随后的功能研究表明，SLC2A11-MIF在体外和体内增强膀胱癌细胞的增殖、抗凋亡作用和转移。从机制上讲，SLC2A11-MIF 编码的融合蛋白与聚嘧啶束结合蛋白 1 (PTBP1) 相互作用，并调节 BCa 细胞中 Polo Like 激酶 1、Roundabout 引导受体 1 和磷酸肌醇 3-激酶调节亚基 3 的 mRNA 半衰期。此外，PTBP1 敲低消除了 SLC2A11-MIF 对生物功能和 mRNA 稳定性的增强影响。此外，SLC2A11-MIF mRNA 的表达受 CCCTC 结合因子调节，并通过 N-乙酰转移酶 10 促进的 RNA N4-乙酰胞苷修饰来稳定。总体而言，我们的研究结果揭示了由 SLC2A11-MIF-PTBP1 轴精心策划的重要融合蛋白，在膀胱癌的多步进展过程中控制 mRNA 稳定性。© 2024 作者。四川国际医学交流中心出版的MedComm

Chimeric RNAs, distinct from DNA gene fusions, have emerged as promising therapeutic targets with diverse functions in cancer treatment. However, the functional significance and therapeutic potential of most chimeric RNAs remain unclear. Here we identify a novel fusion transcript of solute carrier family 2-member 11 (SLC2A11) and macrophage migration inhibitory factor (MIF). In this study, we investigated the upregulation of SLC2A11-MIF in The Cancer Genome Atlas cohort and a cohort of patients from Sun Yat-Sen Memorial Hospital. Subsequently, functional investigations demonstrated that SLC2A11-MIF enhanced the proliferation, antiapoptotic effects, and metastasis of bladder cancer cells in vitro and in vivo. Mechanistically, the fusion protein encoded by SLC2A11-MIF interacted with polypyrimidine tract binding protein 1 (PTBP1) and regulated the mRNA half-lives of Polo Like Kinase 1, Roundabout guidance receptor 1, and phosphoinositide-3-kinase regulatory subunit 3 in BCa cells. Moreover, PTBP1 knockdown abolished the enhanced impact of SLC2A11-MIF on biological function and mRNA stability. Furthermore, the expression of SLC2A11-MIF mRNA is regulated by CCCTC-binding factor and stabilized through RNA N4-acetylcytidine modification facilitated by N-acetyltransferase 10. Overall, our findings revealed a significant fusion protein orchestrated by the SLC2A11-MIF-PTBP1 axis that governs mRNA stability during the multistep progression of bladder cancer.© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.