RAD18 promotes colorectal cancer metastasis by activating the epithelial‑mesenchymal transition pathway

Oncol Rep. 2020 Jul;44(1):213-223. doi: 10.3892/or.2020.7590. Epub 2020 Apr 21.


RAD18 is an E3 ubiquitin‑protein ligase that has a role in carcinogenesis and tumor progression owing to its involvement in error‑prone replication. Despite its significance, the function of RAD18 has not been fully examined in colorectal cancer (CRC). In the present research, by collecting clinical samples and conducting immunohistochemical staining, we found that RAD18 expression was significantly increased in the CRC tissue compared with that noted in the adjacent non‑cancerous normal tissues and that high expression of RAD18 was associated with lymph node metastasis and poor prognosis in CRC patients. In vitro, as determined by cell transfection, scratch, and Transwell experiments, it was also demonstrated that RAD18 increased the invasiveness and migration capacity of CRC cells (HCT116, DLD‑1, SW480). The signaling pathway was analyzed by western blotting and the clinical data were analyzed by immunohistochemical staining and RT‑PCR, indicating that the process of epithelial‑mesenchymal transition (EMT) may be involved in RAD18‑mediated migration and invasion of CRC cells. All of the above data indicate that RAD18 is a novel prognostic biomarker that may become a potential therapeutic target for CRC in the future.

Keywords: RAD18; colorectal cancer; metastasis; epithelialmesenchymal transition.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Up-Regulation*
  • Young Adult


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • RAD18 protein, human
  • Ubiquitin-Protein Ligases