Long non-coding RNAs (LncRNAs) have been suggested as important regulators of cancer development and progression in non-small cell lung cancer (NSCLC). Nevertheless, the biological roles and clinical significance of lncRNA UFC1 in NSCLC remain unclear. We detected the expression of UFC1 in tumor tissues, serum, and serum exosomes of NSCLC patients by qRT-PCR. Gene overexpression or silencing were used to examine the biological roles of UFC1 in NSCLC. RNA immunoprecipitation and ChIP assays were performed to evaluate the interaction between UFC1 and enhancer of zeste homolog 2 (EZH2) and the binding of EZH2 to PTEN gene promoter. Rescue study was used to access the importance of PTEN regulation by UFC1 in NSCLC progression. UFC1 expression was upregulated in tumor tissues, serum, and serum exosomes of NSCLC patients and high level of UFC1 was associated with tumor infiltration. UFC1 knockdown inhibited NSCLC cell proliferation, migration and invasion while promoted cell cycle arrest and apoptosis. UFC1 overexpression led to the opposite effects. Mechanistically, UFC1 bound to EZH2 and mediated its accumulation at the promoter region of PTEN gene, resulting in the trimethylation of H3K27 and the inhibition of PTEN expression. UFC1 knockdown inhibited NSCLC growth in mouse xenograft tumor models while the simultaneous depletion of PTEN reversed this effect. NSCLC cells derived exosomes could promote NSCLC cell proliferation, migration and invasion through the transfer of UFC1. Moreover, Exosome-transmitted UFC1 promotes NSCLC progression by inhibiting PTEN expression via EZH2-mediated epigenetic silencing. Exosome-mediated transmit of UFC1 may represent a new mechanism for NSCLC progression and provide a potential marker for NSCLC diagnosis.

已经提出长非编码RNA（LncRNA）作为非小细胞肺癌（NSCLC）癌症发展和进展的重要调节剂。然而，尚不清楚lncRNA UFC1在NSCLC中的生物学作用和临床意义。我们通过qRT-PCR检测了UFCL1在NSCLC患者的肿瘤组织，血清和血清外泌体中的表达。基因过度表达或沉默被用来检查UFC1在非小细胞肺癌中的生物学作用。进行RNA免疫沉淀和ChIP分析以评估UFC1和zeste同源物2（EZH2）增强子之间的相互作用以及EZH2与PTEN基因启动子的结合。救援研究用于了解UFC1在NSCLC进展中对PTEN调控的重要性。UFC1表达在肿瘤组织，血清，NSCLC患者的血清外泌体和高水平的UFC1与肿瘤浸润有关。UFC1组合式抑制NSCLC细胞增殖，迁移和侵袭，同时促进细胞周期停滞和凋亡。UFC1过表达导致相反的效果。从机制上讲，UFC1与EZH2结合并介导其在PTEN基因启动子区域的积累，从而导致H3K27发生三甲基化并抑制PTEN表达。在老鼠异种移植肿瘤模型中，UFC1抑制可抑制NSCLC的生长，同时PTEN的消耗可逆转此效应。NSCLC细胞衍生的外来体可通过转移UFC1促进NSCLC细胞增殖，迁移和侵袭。此外，外来体传播的UFC1通过EZH2介导的表观遗传沉默抑制PTEN表达，从而促进NSCLC进展。