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

Kaohsiung J Med Sci. 2020 Dec;36(12):983-989. doi: 10.1002/kjm2.12285. Epub 2020 Aug 12.

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.

Keywords: LSCC; SOX2; USP34; cell survival; drug resistance.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm* / drug effects
  • Drug Resistance, Neoplasm* / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • HEK293 Cells
  • Humans
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / pathology*
  • Polyubiquitin / metabolism
  • Protein Binding / drug effects
  • Protein Stability / drug effects
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / pathology*
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism*
  • Ubiquitination / drug effects

Substances

  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Polyubiquitin
  • USP34 protein, human
  • Ubiquitin-Specific Proteases
  • Cisplatin