Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer

Cancer Sci. 2019 Jan;110(1):458-467. doi: 10.1111/cas.13865. Epub 2018 Dec 10.

Abstract

Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) in bladder cancer are still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We carried out immunohistochemistry to explore associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT-qPCR and western blot were used to detect the expressional levels of genes. The biological abilities of cell proliferation, migration and invasion were researched by in vitro and in vivo experiments. Results were as follows: Data from The Cancer Genome Atlas (TCGA) database showed that NEDD8 was overexpressed in BC tissues and was associated with poor patient survival. Results of immunohistochemistry found that NEDD8 was significantly associated with poor clinical outcomes of BC patients. Suppression of NEDD8 could inhibit the proliferation, migration and invasion of tumor cells. Knocking down NEDD8 could induce apoptosis and G2 phase arrest of cell cycle progression. In vivo, suppression of NEDD8 restricted growth and metastasis of tumors in mice. In conclusion, NEDD8 has important roles in regulating the progression of BC cells and was associated with poor prognosis of patients; hence, it may become a potential therapeutic target of BC.

Keywords: NEDD8; bladder cancer; prognosis; tumor progression; tumor tissue.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • NEDD8 Protein / genetics*
  • NEDD8 Protein / metabolism
  • Neoplasm Invasiveness
  • Prognosis
  • RNA Interference
  • RNAi Therapeutics / methods
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / therapy
  • Xenograft Model Antitumor Assays

Substances

  • NEDD8 Protein
  • NEDD8 protein, human