Numb promotes cell proliferation and correlates with poor prognosis in hepatocellular carcinoma

PLoS One. 2014 Apr 25;9(4):e95849. doi: 10.1371/journal.pone.0095849. eCollection 2014.

Abstract

Background: Numb is an evolutionary conserved protein that plays critical roles in cell fate determination, cell adhesion, cell migration and a number of signaling pathways, but evidence for a substantial involvement of Numb in HCC has remained unclear. The present study was aimed to investigate the clinical and prognostic significance of Numb and its role in hepatocellular carcinoma (HCC).

Methodology: The expression of Numb was detected in 107 cases of clinical paraffin-embedded hepatocellular carcinoma tissues,5 matched paris of fresh tissues and six hepatocellular cell lines by immunohistochemistry with clinicopathological analyses,RT-PCR or Western blot. Moreover, loss of function and gain of function assays were performed to evaluate the effect of Numb on cell proliferation in vitro.

Conclusions: We found that Numb was obviously up-regulated in HCC tissues and cell lines (p<0.05). The Numb up-regulation correlated significantly with poor prognosis, and Numb status was identified as an independent prognostic factor. Over-expression of Numb increased proliferation in SMMC-7721 and BEL-7402 cells, while knock-down of Numb showed the opposite effect. Our study indicates that Numb up-regulation significantly correlates with cell proliferation and poor prognosis in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy in hepatocellular carcinoma treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation*
  • Child
  • Female
  • Gene Expression
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Membrane Proteins / physiology*
  • Middle Aged
  • Multivariate Analysis
  • Nerve Tissue Proteins / physiology*
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Up-Regulation
  • Young Adult

Substances

  • Membrane Proteins
  • Nerve Tissue Proteins
  • NUMB protein, human

Grants and funding

This work is supported by grant 81071892 from National Science Foundation of China, and grant S2011010005864 from Natural Science Foundation of Guangdong province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.