Upregulation of UHRF1 promotes the progression of melanoma by inducing cell proliferation

Oncol Rep. 2018 Jun;39(6):2553-2562. doi: 10.3892/or.2018.6356. Epub 2018 Apr 4.

Abstract

Melanoma is the most aggressive cutaneous cancer due to its propensity to metastasise and proliferate. Melanoma accounts for 80‑90% of skin‑cancer related deaths worldwide. Alhough numerous published studies have attempted to define the markers of diagnosis and prognosis of melanoma, a sensitive and specific biomarker for melanoma remains unknown. Recently, ubiquitin‑like with PHD and ring finger domains 1 (UHRF1) has attracted attention due to its role in cell proliferation and it has been deemed as a potential therapeutic target for cancer. The aim of the present study was to investigate the role and the clinical significance of UHRF1 in melanoma. Immunohistochemical analysis was performed with tissue microarray (TMA) to examine the expression of UHRF1 and Ki‑67, and the role of UHRF1 in cell proliferation was determined through CCK‑8, colony formation and flow cytometry by interfering with the expression of UHRF1. Subsequently, the relationship among the expression of UHRF1 and several major clinical characteristics of melanoma were analysed to evaluate the role of UHRF1 in the progression of melanoma. Finally, the clinical significance of UHRF1 was estimated in 56 melanoma patients. It was observed that the expression of UHRF1 was significantly upregulated in melanoma compared with benign nevi tissues (P<0.05). In addition, the downregulation of the expression of UHRF1 significantly decreased cell proliferation. Furthermore, the level of UHRF1 was positively correlated with the expression of Ki‑67 in melanoma cells, as well as in melanoma tissues. Clinically, a high level of UHRF1 was prone to be related to a high TNM classification (P=0.017) and Breslow's thickness (P=0.034) of melanoma. Furthermore, a high level of UHRF1 was positively associated with a shorter overall survival of melanoma patients. Importantly, the Cox regression model analysis demonstrated that the expression of UHRF1 was an independent prognostic factor for the overall survival of melanoma patients. In conclusion, the elevated expression of UHRF1 plays an important role in melanoma cell proliferation and progression, and it can be used as a prognostic biomarker for melanoma.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Neoplasm Staging
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • Survival Analysis
  • Tissue Array Analysis
  • Ubiquitin-Protein Ligases
  • Up-Regulation*

Substances

  • Biomarkers, Tumor
  • CCAAT-Enhancer-Binding Proteins
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases