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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
Author(s) -
Qin Xian-Yang,
Wei Feifei,
Yoshinaga Jun,
Yonemoto Junzo,
Tanokura Masaru,
Sone Hideko
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.09.017
Subject(s) - aryl hydrocarbon receptor nuclear translocator , gene knockdown , aryl hydrocarbon receptor , small interfering rna , biology , downregulation and upregulation , hypoxia inducible factors , microbiology and biotechnology , transcription factor , cancer research , apoptosis , transfection , biochemistry , gene
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.