AEG-1 Promotes Metastasis Through Downstream AKR1C2 and NF1 in Liver Cancer

Oncol Res. 2014;22(4):203-211. doi: 10.3727/096504015X14386062091352.

Abstract

Liver cancer is one of the most lethal cancers, but our knowledge of the molecular mechanism underlying this process remains insufficient. Through deep sequencing and expression regulation analysis in liver cancer cells, we identified two novel factors, AKR1C2 (positive factor) and NF1 (negative factor), as the AEG-1 downstream players in the process of metastasis in liver cancer. They were experimentally validated to have the capacities of regulating cell migration, cell invasion, cell proliferation, and EMT. Further clinic expression and animal model evidence confirmed their functions. Together, our findings provide a new insight into the pharmaceutical and therapeutic use of AEG-1 and downstream AKR1C2 and NF1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / prevention & control
  • Carcinoma, Hepatocellular / secondary
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydroxysteroid Dehydrogenases / genetics
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary
  • Membrane Proteins
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neurofibromin 1 / genetics
  • Neurofibromin 1 / metabolism*
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins
  • RNAi Therapeutics
  • Signal Transduction
  • Time Factors
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • Neurofibromin 1
  • RNA, Messenger
  • RNA-Binding Proteins
  • Hydroxysteroid Dehydrogenases
  • AKR1C2 protein, human