Expression of leucine aminopeptidase 3 (LAP3) correlates with prognosis and malignant development of human hepatocellular carcinoma (HCC)

Int J Clin Exp Pathol. 2014 Jun 15;7(7):3752-62. eCollection 2014.

Abstract

Leucine aminopeptidases (LAPs) were associated with tumor cell proliferation, invasion and/or angiogenesis. LAP3 is one important member of this family. However, its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. In the present study, we demonstrated that LAP3 expression was significantly up-regulated in HCC tissues as well as cells and was closely correlated with lower differentiation, positive lymph node metastasis and high Ki-67 expression, indicating a poor prognosis. Then cell viability assays, flow cytometry assays, wound-healing assays and matrigel invasion assays were performed to demonstrate that LAP3 promoted HCC cells proliferation by regulating G1/S checkpoint in cell cycle and advanced HCC cells migration. Furthermore, we discovered that knockdown LAP3 will enhance the sensitivity of HCC cells to cisplatin, thus promoting the cell death of HCC cells. Collectively, our results indicated that up-regulated expression of LAP3 might contribute to the proliferation and metastasis of HCC. Our data gains greater insight into the cancer-promoting role of LAP3 and its functions in HCC cells, possibly providing potential therapeutic strategies for clinical trials.

Keywords: Hepatocellular carcinoma (HCC); LAP3; migration; prognosis; proliferation.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Blotting, Western
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / pathology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Leucyl Aminopeptidase / biosynthesis*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Prognosis
  • Transfection
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • LAP3 protein, human
  • Leucyl Aminopeptidase