title: Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer.
abstract: Signal transducer and activator of transcription 3 (Stat3) is implicated in the pathogenesis of many malignancies and essential for IL-6-dependent survival and growth of multiple myeloma cells. Here, we demonstrate that the gene encoding oncogenic microRNA-21 (miR-21) is controlled by an upstream enhancer containing 2 Stat3 binding sites strictly conserved since the first observed evolutionary appearance of miR-21 and Stat3. MiR-21 induction by IL-6 was strictly Stat3 dependent. Ectopically raising miR-21 expression in myeloma cells in the absence of IL-6 significantly reduced their apoptosis levels. These data provide strong evidence that miR-21 induction contributes to the oncogenic potential of Stat3.
authors.affiliation: Institute of Clinical Immunology and Transfusion Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Löffler
authors.forename: Katja
authors.initials: K
authors.lastname: Brocke-Heidrich
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pfeifer
authors.forename: Claudia
authors.initials: C
authors.lastname: Stocsits
authors.forename: Jörg
authors.initials: J
authors.lastname: Hackermüller
authors.forename: Antje K
authors.initials: AK
authors.lastname: Kretzschmar
authors.forename: Renate
authors.initials: R
authors.lastname: Burger
authors.forename: Martin
authors.initials: M
authors.lastname: Gramatzki
authors.forename: Conny
authors.initials: C
authors.lastname: Blumert
authors.forename: Kay
authors.initials: K
authors.lastname: Bauer
authors.forename: Helena
authors.initials: H
authors.lastname: Cvijic
authors.forename: A Kerstin
authors.initials: AK
authors.lastname: Ullmann
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.forename: Friedemann
authors.initials: F
authors.lastname: Horn
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D035683:MicroRNAs / Q000502:physiology*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D015850:Interleukin-6; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human