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siRNA-mediated knockdown of aryl hydrocarbon receptor nuclear translocator 2 affects hypoxia-inducible factor-1 regulatory signaling and metabolism in human breast cancer cells.

Abstract
Recent human studies found that the mRNA expression level of aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) was positively associated with the prognosis of breast cancer. In this study, we used small interfering RNA techniques to knockdown ARNT2 expression in MCF7 human breast cancer cells, and found that an almost 40% downregulation of ARNT2 mRNA expression increased the expression of sensitive to apoptosis gene (3.36-fold), and decreased the expression of von Hippel-Lindau (0.27-fold) and matrix metalloproteinase-1 (0.35-fold). The metabolite analysis revealed the contents of glucose, glycine, betaine, phosphocholine, pyruvate and lactate involved in the hypoxia-inducible factor (HIF)-1-dependent glycolytic pathway were significantly lower in cells treated with siARNT2. Our results suggested that ARNT2 might play an important role in the modulation of HIF-1-regulated signaling and metabolism.
AuthorsXian-Yang Qin, Feifei Wei, Jun Yoshinaga, Junzo Yonemoto, Masaru Tanokura, Hideko Sone
JournalFEBS letters (FEBS Lett) Vol. 585 Issue 20 Pg. 3310-5 (Oct 20 2011) ISSN: 1873-3468 [Electronic] England
PMID21945317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Chemical References
  • ARNT2 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Aryl Hydrocarbon Receptor Nuclear Translocator
Topics
  • Aryl Hydrocarbon Receptor Nuclear Translocator (biosynthesis, genetics)
  • Basic Helix-Loop-Helix Transcription Factors (biosynthesis, genetics)
  • Breast Neoplasms (genetics, metabolism)
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Hypoxia-Inducible Factor 1 (genetics, metabolism)
  • Neoplasm Proteins (biosynthesis, genetics)
  • RNA, Small Interfering (genetics, metabolism)
  • Signal Transduction

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