title: miR-214 and hypoxia down-regulate Necl-2/CADM1 and enhance ErbB2/ErbB3 signaling.
abstract: Necl-2/CADM1 is down-regulated by the promoter hypermethylation and/or the loss of heterozygosity at chromosome 11q23.2 in many types of cancers and serves as a tumor suppressor by interacting in cis with ErbB3 and suppressing the ligand-induced ErbB2/ErbB3 signaling for cell movement and death. However, the incidence of these epigenetic and genetic abnormalities of Necl-2 is 30-60% in these cancers. We investigated here other mechanisms that down-regulate Necl-2. miR-214, that is frequently up-regulated in a variety of cancers, targeted the 3'UTR of the Necl-2 mRNA directly, suppressed the translation of Necl-2 and enhanced the ligand-induced ErbB2/ErbB3 signaling in human colon cancer Caco-2 cells. Hypoxia reduced the Necl-2 protein level in a manner independent of miR-214 or hypoxia-inducible factor-1α in Caco-2 cells. These results indicate that miR-214 and hypoxia are novel regulators that down-regulate Necl-2 and enhance ErbB2/ErbB3 signaling.
authors.affiliation: Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Momose
authors.forename: Akihiro
authors.initials: A
authors.lastname: Minami
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimono
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Mizutani
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nobutani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D020413:3' Untranslated Regions; D018938:Caco-2 Cells; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007136:Immunoglobulins; D035683:MicroRNAs; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C403514:CADM1 protein, human; C547397:MIRN214 microRNA, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human