PPPDE1 promotes hepatocellular carcinoma development by negatively regulate p53 and apoptosis

Apoptosis. 2019 Feb;24(1-2):135-144. doi: 10.1007/s10495-018-1491-6.

Abstract

We have previously identified that PPPDE1 is a deubiquitinase (DUB) belonging to a cysteine isopeptidase family. Here we sought to explore the biological significance of PPPDE1 in hepatocellular carcinoma and its underlying molecular mechanism. In the present study, we found that amplification and overexpression of PPPDE1 were associated with poor prognosis in hepatocellular carcinoma (HCC). We also demonstrated that knocking down of PPPDE1 could significantly block the clonal growth and tumorigenicity of human HCC cells, which revealed a critical role for PPPDE1 in HCC development. Furthermore, we proved that PPPDE1 is a key modulator of p53 protein level and its down stream apoptosis pathway. Taken together, these results suggested that PPPDE1 is a putative HCC driver gene and extensive studies should be conducted in the future to investigate the role of PPPDE1 in HCC and other tumors.

Keywords: Apoptosis; Driver gene; Hepatocellular carcinoma; PPPDE1; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Carbon-Nitrogen Lyases / physiology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cohort Studies
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Tumor Suppressor Protein p53 / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Carbon-Nitrogen Lyases
  • DESI2 protein, human