Ubiquitin specific peptidase 47 promotes proliferation of lung squamous cell carcinoma

Genes Genomics. 2022 Jun;44(6):721-731. doi: 10.1007/s13258-022-01233-0. Epub 2022 Mar 7.

Abstract

Background: Ubiquitin specific peptidase 47 (USP47) is a kind of deubiquitinase, which has been reported to play oncogenic roles in several malignancies including colorectal cancer and breast cancer.

Objective: Here we aimed to investigate the clinical significance of USP47 in lung squamous cell carcinoma (LUSC).

Methods: We retrospectively enrolled a cohort of LUSC patients who underwent surgical resection in our hospital (n = 280) and conducted immunohistochemistry staining for their tumor tissues targeting USP47. The correlations between USP47 expression and clinicopathological characteristics were evaluated by Chi-square test. Univariate and multivariate analyses were conducted to assess the prognostic predictive role of USP47 in LUSC. Cell lines and mice models were utilized to explore the tumor-related functions of USP47 in vitro and in vivo, respectively.

Results: Among the 280 cases, there were 127 cases classified as high-USP47 expression and 153 cases with low-USP47 expression. Statistical analyses revealed that higher USP47 expression was independently correlated with larger tumor size, advanced T stage, and unfavorable prognosis. Knockdown of USP47 by shRNA resulted in impaired proliferation of LUSC cell lines and reduced nucleus beta-catenin level. Furthermore, xenograft assays demonstrated that silencing USP47 can inhibit LUSC tumor growth in vivo.

Conclusion: Our research established a novel tumor-promoting effect and prognostic predictive role of USP47 in LUSC, thereby providing evidence for further therapeutic development.

Keywords: Lung squamous cell carcinoma; Prognosis; Proliferation; Ubiquitin specific peptidase 47; Xenografts.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung*
  • Carcinoma, Squamous Cell* / genetics
  • Cell Proliferation / genetics
  • Humans
  • Lung / pathology
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mice
  • Retrospective Studies
  • Ubiquitin Thiolesterase / metabolism*
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism*

Substances

  • USP47 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Proteases