Downregulated Expression of PTPN9 Contributes to Human Hepatocellular Carcinoma Growth and Progression

Pathol Oncol Res. 2016 Jul;22(3):555-65. doi: 10.1007/s12253-015-0038-1. Epub 2015 Dec 29.

Abstract

Human hepatocellular carcinoma (HCC) is one of the most common malignant cancers, whose molecular mechanisms is remains largely. PTPN9 has recently been reported to play a critical role in breast cancer development. However, the role of PTPN9 in human HCC remains elusive. The present study aimed at investigating the potential role of PTPN9 in HCC. Western blot and immunohistochemistry were used to examine the expression of PTPN9 protein in HCC and adjacent non-tumorous tissues in 45 patients. Furthermore, Cell Counting Kit-8, flow cytometry and RNA interference experiments were performed to analyze the role of PTPN9 in the regulation of HCC cell proliferation. We showed that the expression level of PTPN9 was significantly reduced in HCC, compared with adjacent non-tumorous tissues. PTPN9 expression was inversely associated with Tumor size (P = 0.014), serum AFP level (P = 0.004) and Ki-67 expression. Low expression of PTPN9 predicted poor survival in HCC patients. Moreover, PTPN9 interference assay that PTPN9 inhibited cell proliferation in HepG2 cells. Cell apoptosis assay revealed that, silencing of PTPN9 expression significantly reduced cell apoptosis, compared with control ShRNA treatment group. Our results suggested that PTPN9 expression was down-regulated in HCC tumor tissues, and reduced PTPN9 expression was associated with worsened overall survival in HCC patients. Depletion of PTPN9 inhibits the apoptosis and promotes the proliferation of HCC cells.

Keywords: Cell proliferation; Human hepatocellular carcinoma (HCC); PTPN9; Prognosis.

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Disease Progression
  • Down-Regulation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics*

Substances

  • Biomarkers, Tumor
  • PTPN9 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor