超级增强子（SE）是与细胞特性和疾病相关的调控元素簇。虽然对于肺腺癌（LUAD）中与SE相关的长非编码RNA（lncRNA）功能的研究还很少，但在我们的研究中发现了一个由SE驱动的lncRNA，LINC00880，在LUAD中的表达高于正常组织，并且在I期LUAD患者中预示着不良预后。我们发现转录因子（TF）FOXP3能够同时结合LINC00880的启动子和SE区域来促进其转录。通过体外和体内实验证实了LINC00880的致癌功能。在机制上，LINC00880结合蛋白质CDK1以增加其激酶活性，这依赖于CDK1中pT161的磷酸化状态。LINC00880还促进了CDK1和PRDX1之间的相互作用。此外，LINC00880与PRDX1相互作用，表明LINC00880充当了CDK1和PRDX1之间的蛋白质支架，形成三部分复合物，从而激活PI3K/AKT通路来促进恶性。我们的研究结果揭示了SE相关的lncRNA LINC00880通过调控CDK1/PRDX1轴来维持LUAD的恶性，为新的治疗靶点提供了基础。© 2023. 作者。

Super-enhancers (SEs) are regulatory element clusters related to cell identity and disease. While the studies illustrating the function of SE-associated long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) remains few. In our research, a SE-driven lncRNA, LINC00880, was identified, which showed higher expression in LUAD compared to normal tissues and indicated worse outcomes in stage I LUADs. We found that the transcription factor (TF) FOXP3 could simultaneously occupy the promoter and SE regions of LINC00880 to promote its transcription. The oncogenic function of LINC00880 was validated both in vitro and in vivo. Mechanically, LINC00880 binds to the protein CDK1 to increase its kinase activity, which rely on the phosphorylation state of pT161 in CDK1. LINC00880 also promotes the interaction between CDK1 and PRDX1. Moreover, LINC00880 interacts with PRDX1, which indicates that LINC00880 acts as a protein scaffold between CDK1 and PRDX1 to form a ternary complex, thereby resulting in the activation of PI3K/AKT to promote malignancy. Our results reveal that the SE-associated lncRNA LINC00880 regulates the CDK1/PRDX1 axis to sustain the malignancy of LUAD, providing a novel therapeutic target.© 2023. The Author(s).