The deubiquitinase USP34 stabilizes SOX2 and induces cell survival and drug resistance in laryngeal squamous cell carcinoma

Abstract

Recent studies showed that the deubiquitinase ubiquitin‐specific protease 34 (USP34) was involved in the tumorigenesis of several tumors, but its function and mechanism are still unclear in laryngeal squamous cell carcinoma (LSCC). In this study, we found that USP34 and SOX2 were elevated in LSCC tumor tissues, and we also found that USP34 expression was positively correlated with SOX2 expression. Our further studies showed that USP34 regulated the protein level of SOX2 in LSCC cells, but not the mRNA level, which suggested that USP34 stabilized SOX2. Moreover, USP34, as a deubiquitinase, could interact with SOX2, and reduce the polyubiquitination of SOX2. In addition, knockdown of USP34 could significantly inhibit LSCC cell growth, but overexpression of SOX2 could reverse this effect. Finally, we also found that USP34 and SOX2 were upregulated in cisplatin‐resistant LSCC cells, but knockdown of USP34 could enhance the drug sensitivity of cisplatin in the resistant cells. Collectively, targeting USP34/SOX2 axis may be a promising strategy for the treatment of LSCC.

Knockdown of deubiquitinating enzyme Usp34 confers resistance to methylmercury in HEK293 cells

“…Usp34 negatively regulates ubiquitination of gp78 and Sox2, thereby inhibiting their degradation in the proteasome (Dai et al, 2020;Wang et al, 2019). gp78 is a ubiquitin ligase involved in endoplasmic reticulum-associated degradation, which is protective against endoplasmic reticulum stress (Shen et al, 2006;Zhong et al, 2004).…”

MicroRNAs regulating SOX2 in cancer progression and therapy response

“…The ubiquitin-specific protease 34 (USP34) is a deubiquitinase that can induce cisplatin (CP) resistance in laryngeal carcinoma cells by upregulating SOX2 expression and promoting cancer growth and survival (Ref. 88). The SOX2 down-regulation by histone deacetylase 11 (HDAC11) inhibitors impairs self-renewal capability and enhances chemosensitivity (Ref.…”