Overexpression of WWP1 promotes tumorigenesis and predicts unfavorable prognosis in patients with hepatocellular carcinoma

Oncotarget. 2015 Dec 1;6(38):40920-33. doi: 10.18632/oncotarget.5712.


WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) has been speculated to play important roles in the development of several kinds of cancers. However, the role of WWP1 in hepatocellular carcinoma(HCC) is not clear. In the present study, we investigated the expression and prognostic role of WWP1 in primary hepatocellular carcinoma (HCC) using cell lines and 149 archived HCC samples. Correlation between the functions of WWP1 in HCC was also explored. We used human HCC cell lines (BEL-7402, SMMC-7721, Hep-G2, Hep-3B, SK-hep1 and Huh7) and a normal hepatocyte cell line (LO2) along with HCC samples from patients who had undergone resection for HCC previously at our hospital. A battery of methods (real-time quantitative polymerase chain reaction; western blotting; immunohistochemical analyses; cell proliferation and colony formation assays; cell migration and cell invasion assays) were employed to assess various aspects of WWP1. We found that WWP1 expression was upregulated aberrantly at mRNA and protein levels in human primary HCC tissues. Amplified expression of WWP1 was highly correlated with poor outcome. Silencing of WWP1 expression by siRNA inhibited the proliferation, colony formation, migration and invasion of HCC cells in vitro, and resulted in significant apoptosis and cycle arrest in HCC cells. Our findings suggest that WWP1 might have an oncogenic role in human primary HCC, and that it could be used as a prognostic marker as well as a potential molecular target for the treatment of HCC.

Keywords: WWP1; hepatocellular carcinoma; oncogene; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tumor Cells, Cultured
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Young Adult


  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Small Interfering
  • WWP1 protein, human
  • Ubiquitin-Protein Ligases