USP21 contributes to the aggressiveness of laryngeal cancer cells by deubiquitinating and stabilizing AURKA

Abstract

AbstractLaryngeal 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.