Lung adenocarcinoma (LUAD), a histological subclass of non-small-cell lung cancer, is globally the leading cause of cancer-related deaths. Long noncoding RNAs (lncRNAs) are emerging as cancer regulators. Zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) is an oncogene in gastric cancer, but its functions have not been investigated in LUAD. We showed that ZFPM2-AS1 expression is high in LUAD samples based on GEPIA database (http://gepia.cancer-pku.cn/) and validated ZFPM2-AS1 upregulation in LUAD cell lines. Functionally, ZFPM2-AS1 facilitated proliferation, invasion, and epithelial-to-mesenchymal transition of LUAD cells. Thereafter, we found that ZFPM2 was negatively regulated by ZFPM2-AS1, and identified the suppressive effect of ZFPM2 regulation by ZFPM2-AS1 on LUAD progression. Mechanistically, we showed that ZFPM2-AS1 interacted with up-frameshift 1 (UPF1) to regulate mRNA decay of ZFPM2. Rescue assays in vitro and in vivo confirmed that ZFPM2-AS1 regulated LUAD progression and tumor growth through ZFPM2. Taken together, our findings demonstrate a role for the ZFPM2-AS1-UPF1-ZFPM2 axis in LUAD progression, suggesting ZFPM2-AS1 as a new potential target for LUAD treatment.

中文翻译：

---

LncRNA ZFPM2-AS1通过与UPF1相互作用使ZFPM2不稳定来促进肺腺癌的进展。

肺腺癌（LUAD）是非小细胞肺癌的组织学子类别，在全球范围内是癌症相关死亡的主要原因。长的非编码RNA（lncRNA）逐渐成为癌症的调节剂。锌指蛋白多型2反义RNA 1（ZFPM2-AS1）是胃癌的癌基因，但尚未在LUAD中研究其功能。我们基于GEPIA数据库（http://gepia.cancer-pku.cn/）展示了LUAD样品中ZFPM2-AS1的表达较高，并验证了LUAD细胞系中ZFPM2-AS1的上调。在功能上，ZFPM2-AS1促进LUAD细胞的增殖，侵袭和上皮向间充质转化。此后，我们发现ZFPM2被ZFPM2-AS1负调控，并确定ZFPM2-AS1对ZADPM的抑制对LUAD进展的抑制作用。机械上，我们显示ZFPM2-AS1与向上移码1（UPF1）相互作用以调节ZFPM2的mRNA衰减。体外和体内的拯救试验证实，ZFPM2-AS1通过ZFPM2调节LUAD进程和肿瘤生长。综上所述，我们的发现证明ZFPM2-AS1-UPF1-ZFPM2轴在LUAD进展中发挥了作用，表明ZFPM2-AS1是LUAD治疗的新潜在靶标。