title: 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.
authors.affiliation: Health Risk Research Section, Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. y_qin@envhlth.k.u-tokyo.ac.jp
authors.forename: Xian-Yang
authors.initials: XY
authors.lastname: Qin
authors.forename: Feifei
authors.initials: F
authors.lastname: Wei
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshinaga
authors.forename: Junzo
authors.initials: J
authors.lastname: Yonemoto
authors.forename: Masaru
authors.initials: M
authors.lastname: Tanokura
authors.forename: Hideko
authors.initials: H
authors.lastname: Sone
mesh_terms: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000096:biosynthesis* / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D051793:Hypoxia-Inducible Factor 1; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C490989:ARNT2 protein, human