非小细胞肺癌（NSCLC）是一种全球范围内致命的疾病。我们发现，来自伪基因的长链非编码RNA（lncRNA）PTTG3P在NSCLC中被上调表达，并与肿瘤体积增大、晚期分期和恶劣预后相关。本研究调查了PTTG3P在NSCLC中的致癌作用及其机制。我们证明，在体外和体内，PTTG3P促进了NSCLC细胞的增殖、迁移、肿瘤形成和转移，同时抑制了凋亡。在机制上，PTTG3P与ILF3形成RNA-蛋白复合物，维持了MAP2K6和E2F1 mRNA的稳定性，这两个是参与NSCLC进展的致癌因子。RNA-seq显示，在PTTG3P沉默时，MAP2K6和E2F1被下调。RIP和RNA稳定性实验显示，PTTG3P/ILF3相互作用稳定了MAP2K6和E2F1的转录本。有趣的是，E2F1通过结合PTTG3P的启动子而转录上调PTTG3P，形成一个正反馈环路。沉默E2F1或PTTG3P减弱了它们对细胞生长和迁移的相互调控影响。因此，PTTG3P/ILF3/E2F1轴增强了致癌基因表达，促进了NSCLC的发病机制。我们的研究揭示了PTTG3P通过mRNA稳定和反馈回路在NSCLC中发挥致癌功能，突显其作为预后生物标志物和治疗靶点的潜力。© 作者

Non-small cell lung cancer (NSCLC) is a highly lethal disease worldwide. We found the pseudogene-derived lncRNA PTTG3P is upregulated in NSCLC and associated with larger tumor size, advanced staging, and poor prognosis. This study investigated the oncogenic roles and mechanisms of PTTG3P in NSCLC. We demonstrate that PTTG3P promoted NSCLC cell proliferation, migration, tumorigenesis, and metastasis while inhibiting apoptosis in vitro and in vivo. Mechanistically, PTTG3P formed an RNA-protein complex with ILF3 to maintain MAP2K6 and E2F1 mRNA stability, two oncogenic factors involved in NSCLC progression. RNA-seq revealed MAP2K6 and E2F1 were downregulated upon PTTG3P knockdown. RIP and RNA stability assays showed PTTG3P/ILF3 interaction stabilized MAP2K6 and E2F1 transcripts. Interestingly, E2F1 transcriptionally upregulated PTTG3P by binding its promoter, forming a positive feedback loop. Knockdown of E2F1 or PTTG3P attenuated their mutual regulatory effects on cell growth and migration. Thus, a PTTG3P/ILF3/E2F1 axis enhances oncogene expression to promote NSCLC pathogenesis. Our study reveals PTTG3P exerts oncogenic functions in NSCLC via mRNA stabilization and a feedback loop, highlighting its potential as a prognostic biomarker and therapeutic target.© The author(s).