Department of Anesthesiology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang Province, People's Republic of China.
Department of Otolaryngology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang Province, People's Republic of China.
Kaohsiung J Med Sci. 2023 Apr;39(4):354-363. doi: 10.1002/kjm2.12649. Epub 2023 Mar 15.
Laryngeal cancer is a usual malignant tumor of the head and neck. The role and mechanism of deubiquitinase USP21 in laryngeal cancer are still unclear. We aimed to explore whether USP21 affected laryngeal cancer progress through deubiquitinating AURKA. USP21 and AURKA levels were evaluated by qRT-PCR and Western blot. Kaplan-Meier analysis was conducted by survival package. MTT was performed to detect cell proliferation. The wound healing assay was applied to evaluate cell migration. Transwell was used to measure cell invasion. Co-IP and GST-pull down determined the interaction between USP21 and AURKA. In addition, AURKA ubiquitination levels were analyzed. USP21 was signally elevated in laryngeal cancer tissues and cells. USP21 level in clinical stages III-IV was higher than that in clinical stages I-II, and high levels of USP21 were highly correlated with poor prognosis in laryngeal cancer. USP21 inhibition suppressed AMC-HN-8 and TU686 cell proliferation, migration and invasion. Co-IP and GST-pull down confirmed the interaction between USP21 and AURKA. Knockdown of USP21 markedly increased the ubiquitination level of AURKA, and USP21 restored AURKA activity through deubiquitination. In addition, overexpression of AURKA reversed the effects of USP21 knockdown on cell growth, migration, and invasion. USP21 stabilized AURKA through deubiquitination to promote laryngeal cancer progression.
喉癌是头颈部常见的恶性肿瘤。去泛素化酶 USP21 在喉癌中的作用和机制尚不清楚。本研究旨在探讨 USP21 是否通过去泛素化 AURKA 影响喉癌的进展。通过 qRT-PCR 和 Western blot 评估 USP21 和 AURKA 水平。通过生存包进行 Kaplan-Meier 分析。通过 MTT 检测细胞增殖。通过划痕愈合实验评估细胞迁移。通过 Transwell 测量细胞侵袭。通过 Co-IP 和 GST-pull down 确定 USP21 和 AURKA 之间的相互作用。此外,分析 AURKA 泛素化水平。USP21 在喉癌组织和细胞中显著上调。临床分期 III-IV 期的 USP21 水平高于临床分期 I-II 期,且 USP21 高水平与喉癌预后不良高度相关。USP21 抑制抑制 AMC-HN-8 和 TU686 细胞增殖、迁移和侵袭。Co-IP 和 GST-pull down 证实了 USP21 和 AURKA 之间的相互作用。USP21 的敲低显著增加了 AURKA 的泛素化水平,USP21 通过去泛素化恢复了 AURKA 的活性。此外,AURKA 的过表达逆转了 USP21 敲低对细胞生长、迁移和侵袭的影响。USP21 通过去泛素化稳定 AURKA 以促进喉癌进展。