The silencing of Pokemon attenuates the proliferation of hepatocellular carcinoma cells in vitro and in vivo by inhibiting the PI3K/Akt pathway

PLoS One. 2012;7(12):e51916. doi: 10.1371/journal.pone.0051916. Epub 2012 Dec 26.

Abstract

Pokemon (POK erythroid myeloid ontogenic factor), which belongs to the POK protein family, is also called LRF, OCZF and FBI-1. As a transcriptional repressor, Pokemon assumes a critical function in cellular differentiation and oncogenesis. Our study identified an oncogenic role for Pokemon in human hepatocellular carcinoma (HCC). We successfully established human HepG2 and Huh-7 cell lines in which Pokemon was stably knocked down. We demonstrated that Pokemon silencing inhibited cell proliferation and migration. Pokemon knockdown inhibited the PI3K/Akt and c-Raf/MEK/ERK pathways and modulated the expression of various cell cycle regulators in HepG2 and Huh-7 cells. Therefore, Pokemon may also be involved in cell cycle progression in these cells. We confirmed that Pokemon silencing suppresses hepatocellular carcinoma growth in tumor xenograft mice. These results suggest that Pokemon promotes cell proliferation and migration in hepatocellular carcinoma and accelerates tumor development in an Akt- and ERK-signaling-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / prevention & control*
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • In Vitro Techniques
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / prevention & control*
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Nude
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Wound Healing
  • Xenograft Model Antitumor Assays

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Transcription Factors
  • ZBTB7A protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by Youth Innovation Fund of Fujian Province (2006F3127), National Natural Science Foundation of China (No. 30971362 & 81072013) and Fundamental Research Funds for the Central Universities in China (No. 2010111082). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.