Up-regulation of microRNA-155 promotes cancer cell invasion and predicts poor survival of hepatocellular carcinoma following liver transplantation

J Cancer Res Clin Oncol. 2012 Jan;138(1):153-61. doi: 10.1007/s00432-011-1076-z. Epub 2011 Nov 10.


Purpose: MicroRNAs play important roles in cancer development, progression, and metastasis. The aim of this study was to determine whether altered microRNA-155 expression is associated with hepatocellular carcinoma (HCC) recurrence and prognosis following orthotopic liver transplantation (OLT).

Methods: Tissue specimens from 100 HCC patients following OLT were recruited. MicroRNA-155 expression levels were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of microRNA-155 expression with survival of patients. MicroRNA-155 expression levels of two HCC cell lines (HepG2 and SMMC-7721) and normal liver tissue were quantified using qRT-PCR. The potential function of miR-155 on invasiveness was evaluated in the above HCC cell lines.

Results: We found that microRNA-155 expression levels were high in tumor tissues in patients with post-OLT HCC recurrence (n = 45) compared with those in patients with non-recurrence (n = 55) (P = 0.001) and correlated with micro-vascular invasion of HCC tissue samples (P = 0.001). Patients with higher miR-155 expression had significantly poorer recurrence-free survival (RFS, log rank P < 0.001) and overall survival (OS, log rank P < 0.001). Multivariate analysis revealed that high miR-155 expression was an independent predictor of poor prognosis (HR 2.748, P = 0.001 for RFS; HR 5.752, P < 0.001 for OS). In addition, the invasiveness of HCC cells was significantly increased by higher microRNA-155 expression.

Conclusions: MicroRNA-155 is a candidate oncogenic microRNA and plays an important role in promoting HCC cells invasion. Our findings suggest that microRNA-155 may serve as a novel biomarker for tumor recurrence and survival of HCC patients following OLT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery*
  • Cell Line, Tumor
  • Disease-Free Survival
  • Female
  • Humans
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery*
  • Liver Transplantation*
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Transfection
  • Up-Regulation


  • Biomarkers, Tumor
  • MIRN155 microRNA, human
  • MicroRNAs