Expression and prognostic impact of PRL-3 in lymph node metastasis of gastric cancer: its molecular mechanism was investigated using artificial microRNA interference

Int J Cancer. 2008 Sep 15;123(6):1439-47. doi: 10.1002/ijc.23643.

Abstract

High PRL-3 expression had been reported to have close association with lymph node metastasis (LNM) of gastric cancer. However, the prognostic significance of highly expressing PRL-3 in LNM of human gastric cancer and the role in the metastasis remain unclear. Our study examined PRL-3 expression both in the LNM (n = 107) and in the primary lesion (n = 137) of gastric cancer, and compared the overall survival rates. RNA interference, induced by recombinant plasmid pcDNA.rPRL3-miR expressing artificial PRL-3 miRNA, was employed to knockdown PRL-3 expression in human SGC7901 gastric cancer cells. Invasion assay and migration assay in vitro were conducted to determine the role of PRL-3 in the metastasis. The role of PRL-3 in the proliferation of SGC7901 cells and tumor growth were also determined. We observed that high PRL-3 expression was more frequently detected in the LNM than in the matched primary lesion (72.9 vs. 47.7%, p < 0.001). Furthermore, the overall survival rate of the patients with high expression of PRL-3 in the LNM was significantly less than those with moderate/low expression (p = 0.003). Importantly, knockdown of PRL-3 can significantly reduce both invasion and migration potencies of SGC7901 cells (p < 0.001), and significantly suppressed the proliferation of SGC7901 cells and slowed down the tumor growth (p < 0.001). It was concluded that high expression of PRL-3 in the LNM had a negative impact on the prognosis of the patients, and plays important roles in LNM of gastric cancer and the tumor growth, which can be a potential therapeutic target and a prognostic factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Blotting, Western
  • Cell Line, Tumor
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology*
  • Male
  • MicroRNAs
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Prognosis
  • Protein Tyrosine Phosphatases / biosynthesis*
  • Protein Tyrosine Phosphatases / genetics
  • RNA Interference*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Transfection

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • Neoplasm Proteins
  • PTP4A3 protein, human
  • Protein Tyrosine Phosphatases