title: Iron-mediated stability of PAI-1 mRNA in adenocarcinoma cells-involvement of a mRNA-binding nuclear protein.
abstract: This study reports the stability of mRNA of type-1 plasminogen activator inhibitor (PAI-1), the major physiologic inhibitor of plasminogen activation, by deferoxamine-aided iron deprivation, in PC3 adenocarcinoma cells. ELISA and Northern analyses studies revealed dose-dependent increase in PAI-1 expression by deferoxamine-treated cells. Co-treatment with ferric citrate quenched the effect of deferoxamine, confirming the role of iron in PAI-1 regulation. DRB-based RNA chase experiments suggested that post-transcriptional mechanism was involved in PAI-1 regulation. De-novo protein synthesis was necessary for this regulation. Electrophoretic mobility shift assay revealed the presence of a nuclear protein, binding to the 3'-UTR of PAI-1 mRNA in an iron-mediated manner. This is the first report of iron-mediated mRNA-protein interaction in PAI-1, involved in mRNA stability.
authors.affiliation: Department of Physiology, Miyazaki Medical College, Kihara 5200, Kiyotake-cho, Miyazaki 889-1692, Japan. radharao@med.miyazaki-u.ac.jp
authors.forename: K S
authors.initials: KS
authors.lastname: Radha
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugiki
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Harish Kumar
authors.forename: Sayuri
authors.initials: S
authors.lastname: Omura
authors.forename: Masugi
authors.initials: M
authors.lastname: Maruyama
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D003676:Deferoxamine / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D009687:Nuclear Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C025314:ferric citrate; D007501:Iron; D003676:Deferoxamine