The roles of long noncoding RNA (lncRNA) MACC1-AS1 have been revealed in various tumors. This work aims to explore the roles of lncRNA MACC1-AS1 in the stemness of nonsmall cell lung cancer (NSCLC) cells and the underlying mechanism. We showed that overexpression of MACC1-AS1 enhanced the stemness of NSCLC cells, which is evident as the increased expression of cancer stem cell transcription factors, ALDH1 activity, and sphere-formation capacity, while knockdown of MACC1-AS1 decreased it. RNA-sequencing analysis revealed that the Hippo pathway was mostly enriched in NSCLC cell with MACC1-AS1 overexpression. Further mRNA and western blot analysis showed that ectopic expression of MACC1-AS1 regulated the expression LATS1/2, the critical regulator of Hippo pathway. Additionally, it was found that MACC1-AS1 interacted with up-frameshift 1 (UPF1) to modulate mRNA decay of LATS1/2. Overexpression of LAST1/2 attenuated the promoting effects of MACC1-AS1 overexpression on the stemness of NSCLC cells. Therefore, our results demonstrate the effects of the novel MACC1-AS1/UPF1/LATS1/2 axis in NSCLC cell stemness.

中文翻译：

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长链非编码 RNA MACC1-AS1 通过促进 UPF1 介导的 LATS1 /2 失稳促进非小细胞肺癌细胞的干性

长链非编码 RNA (lncRNA) MACC1-AS1 在各种肿瘤中的作用已被揭示。本工作旨在探讨lncRNA MACC1-AS1在非小细胞肺癌（NSCLC）细胞干性中的作用及其潜在机制。我们发现 MACC1-AS1 的过表达增强了 NSCLC 细胞的干性，这在癌症干细胞转录因子、ALDH1 活性和球形成能力的表达增加方面是显而易见的，而 MACC1-AS1 的敲低则降低了它。RNA 测序分析显示 Hippo 通路主要富集于 MACC1-AS1 过表达的 NSCLC 细胞中。进一步的 mRNA 和蛋白质印迹分析表明 MACC1-AS1 的异位表达调节了 Hippo 通路的关键调节因子 LATS1/2 的表达。此外，发现 MACC1-AS1 与上移码 1 (UPF1) 相互作用以调节 LATS1/2 的 mRNA 衰减。LAST1/2的过表达减弱了MACC1-AS1过表达对NSCLC细胞干性的促进作用。因此，我们的结果证明了新型 MACC1-AS1/UPF1/LATS1/2 轴在 NSCLC 细胞干细胞中的作用。