Ubiquitin specific peptidase 19 is a prognostic biomarker and affect the proliferation and migration of clear cell renal cell carcinoma

Oncol Rep. 2020 Jun;43(6):1964-1974. doi: 10.3892/or.2020.7565. Epub 2020 Mar 26.

Abstract

Ubiquitin specific peptidase 19 (USP19) is a member of the USP family and exhibits diverse roles in various biological processes, such as cell differentiation, cell cycle progression and apoptosis. There is limited knowledge regarding the role and impact of USP19 in cancer, particularly clear cell renal cell carcinoma (ccRCC). To examine the function of USP19 in ccRCC, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases were examined to determine USP19 mRNA expression levels. USP19 mRNA levels were significantly lower in ccRCC tissues than in normal tissues. USP19 downregulation was associated with ccRCC progression and poor prognostic outcomes in TCGA cohort. Furthermore, the functional involvement of USP19 in ccRCC was examined using Cell Counting Kit‑8, soft agar, Transwell and wound healing assays in vitro following overexpression or knockdown of USP19 in the Caki‑1 cell line. USP19 overexpression inhibited ccRCC proliferation and migration, whereas USP19 knockdown promoted ccRCC proliferation and migration in vitro. Consistent with these results, it was further demonstrated that USP19 downregulation promoted tumor growth in vivo in a xenograft model. Mechanistically, it was found that USP19 exerted its inhibitory effect on ccRCC proliferation and migration by suppressing the activation of ERK. Collectively, the present findings identified a role for USP19 as a tumor suppressor in ccRCC and demonstrated that USP19 is a potential prognostic biomarker that could be applied in ccRCC therapy.

Keywords: ubiquitin specific peptidase 19; clear cell renal cell carcinoma; suppressor; proliferation; migration.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Disease Progression
  • Down-Regulation
  • Endopeptidases / genetics*
  • Endopeptidases / metabolism*
  • Female
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Mice
  • Neoplasm Transplantation
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Endopeptidases
  • USP19 protein, human