肺癌是全球癌症相关死亡的主要原因。长非编码RNA（lncRNA）已被认为是癌症发展和进展的关键调节因子，也是癌症诊断和预后的有希望生物标记物。在本研究中，我们发现一种新的lncRNA（LINC02159），其在非小细胞肺癌（NSCLC）患者的肿瘤组织和血清中上调表达。我们证明，LINC02159的敲除抑制了NSCLC细胞的增殖、迁移和侵袭，同时诱导细胞凋亡和细胞周期阻滞；体外实验显示了抑癌作用，生物实验表明延缓了肿瘤生长，而LINC02159的过表达则产生了相反的效果。通过转录组分析，我们发现LINC02159与癌症生长和转移相关的信号通路高度相关，并确定YAP1是LINC02159的潜在靶基因。机制研究发现，LINC02159通过与Aly/REF运输因子（ALYREF）结合，通过m5C修饰增强了YAP1信使RNA（mRNA）的稳定性，导致NSCLC细胞中YAP1的过表达，激活Hippo和β-连环蛋白信号通路。救治实验证实了LINC02159以YAP1和ALYREF为依赖因子促进NSCLC的进展。总之，LINC02159通过调节ALYREF/YAP1信号通路在NSCLC进展中发挥了致癌作用，并有潜力作为NSCLC的诊断标志物和治疗靶点。© 2023. BioMed Central Ltd., part of Springer Nature.

Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have emerged as key regulators of cancer development and progression, and as promising biomarkers for the diagnosis and prognosis of cancer. In this study, we identified a new lncRNA (LINC02159) that was upregulated in the tumor tissues and serum of non-small cell lung cancer (NSCLC) patients. We demonstrated that knockdown of LINC02159 inhibited NSCLC cell proliferation, migration, and invasion, but induced cell apoptosis and cell cycle arrest in vitro and retarded tumor growth in vivo, while overexpression of LINC02159 led to the opposite effect. We discovered that LINC02159 was highly correlated with cancer growth and metastasis-related pathways by using transcriptomic analysis and that YAP1 was a potential target gene of LINC02159. Mechanistically, LINC02159 bound to the Aly/REF export factor (ALYREF) to enhance the stability of YAP1 messenger RNA (mRNA) via m5C modification, which led to the overexpression of YAP1 and the activation of the Hippo and β-catenin signaling pathways in NSCLC cells. Rescue experiments showed that LINC01259 promoted NSCLC progression in a YAP1- and ALYREF-dependent manner. In conclusion, LINC02159 plays an oncogenic role in NSCLC progression by regulating ALYREF/YAP1 signaling, and it has the potential to be utilized as a diagnostic marker and therapeutic target for NSCLC.© 2023. BioMed Central Ltd., part of Springer Nature.