Using a yeast two-hybrid system to identify FTCD as a new regulator for HIF-1α in HepG2 cells

Cell Signal. 2014 Jul;26(7):1560-6. doi: 10.1016/j.cellsig.2014.03.016. Epub 2014 Mar 29.

Abstract

HIF-1α is implicated in hepatocellular carcinoma (HCC) pathologies. Here, we screened a human liver cDNA library for HIF-1α-interacting partners using a yeast two-hybrid system. We identified 53 genes, including formiminotransferase cyclodeaminase (FTCD), which was confirmed by co-immunoprecipitation. Moreover, our data indicated that HIF-1α mediated the effects of hypoxia on FTCD induction via binding to the hypoxia-responsive elements of the FTCD promoter. Knockdown of FTCD reduced the effects of HIF-1α in hypoxia and enhanced chemosensitivity in HepG2 cells. Our findings suggested crosstalk between FTCD and HIF signaling and promoted HCC progression, thus implicating FTCD as a therapeutic target for HCC.

Keywords: Chemosensitivity; FTCD; HIF-1α; Hypoxia; Yeast two-hybrid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonia-Lyases / biosynthesis
  • Ammonia-Lyases / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Hypoxia / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • Glutamate Formimidoyltransferase / biosynthesis
  • Glutamate Formimidoyltransferase / metabolism*
  • Hep G2 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Liver Neoplasms / pathology*
  • Multifunctional Enzymes
  • Neoplasm Invasiveness / pathology
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering
  • Response Elements / genetics
  • Signal Transduction
  • Two-Hybrid System Techniques*

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Multifunctional Enzymes
  • RNA, Small Interfering
  • FTCD protein, human
  • Glutamate Formimidoyltransferase
  • Ammonia-Lyases