Deubiquitinases (DUBs) and noncoding RNAs have been the subjects of recent extensive studies regarding their roles in lung cancer, but the mechanisms involved are largely unknown. In our study, we used The Cancer Genome Atlas data set and bioinformatics analyses and identified USP21, a DUB, as a potential contributor to oncogenesis in non-small-cell lung cancer (NSCLC). We further demonstrated that USP21 was highly expressed in NSCLCs. We then conducted a series of in vitro and in vivo assays to explore the effect of USP21 on NSCLC progression and the underlying mechanism involved. USP21 promoted NSCLC cell proliferation, migration, and invasion and in vivo tumor growth by stabilizing a well-known oncogene, Yin Yang-1 (YY1), via mediating its deubiquitination. Furthermore, YY1 transcriptionally regulates the expression of SNHG16. Moreover, StarBase bioinformatics analyses predicted that miR-4500 targets SNHG16 and USP21. A series of in vitro experiments indicated that SNHG16 increased the expression of USP21 through miR-4500. In summary, the USP21/YY1/SNHG16 axis plays a role in promoting the progression of NSCLC. Therefore, the USP21/YY1/SNHG16/miR-4500 axis may be a potential therapeutic target in NSCLC treatment.

去泛素化酶 (DUB) 和非编码 RNA 一直是最近关于它们在肺癌中作用的广泛研究的主题，但所涉及的机制在很大程度上是未知的。在我们的研究中，我们使用癌症基因组图谱数据集和生物信息学分析并确定 USP21（一种 DUB）是非小细胞肺癌 (NSCLC) 肿瘤发生的潜在因素。我们进一步证明 USP21 在 NSCLC 中高表达。然后，我们进行了一系列体外和体内试验，以探索 USP21 对 NSCLC 进展的影响以及所涉及的潜在机制。USP21通过介导其去泛素化来稳定众所周知的癌基因Yin Yang-1 (YY1)，从而促进NSCLC细胞增殖、迁移和侵袭以及体内肿瘤生长。此外，YY1 转录调节 SNHG16 的表达。而且，StarBase 生物信息学分析预测 miR-4500 靶向 SNHG16 和 USP21。一系列体外实验表明，SNHG16 通过 miR-4500 增加 USP21 的表达。综上所述，USP21/YY1/SNHG16轴在促进NSCLC进展中发挥作用。因此，USP21/YY1/SNHG16/miR-4500轴可能是NSCLC治疗的潜在治疗靶点。