The USP21/YY1/SNHG16 axis contributes to tumor proliferation, migration, and invasion of non-small-cell lung cancer

Lung cancer: Targeting a vicious circle Therapies targeting a molecular feedback loop involved in tumor growth may prove valuable for treating non-small-cell lung cancer. Fangbao Ding, Jianbing Huang, and co-workers at Shanghai Jiao Tong University in Shanghai, China, have shown how an enzyme called USP21 promotes cancer cell proliferation and tumor growth in non-small-cell lung cancer. The team took cancerous and non-cancerous lung tissue samples from 42 patients, and analyzed the expression and behavior of USP21. The enzyme was highly expressed in cancerous tissues, where it stabilized a known gene with the potential to cause cancer called YY1. This gene also regulated the expression of a particular RNA molecule, which in turn worked to increase levels of USP21. This cyclical process encouraged the proliferation, migration and invasion of non-small-cell lung cancer cells, and may provide a future therapeutic target. 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.