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  • Interleukin-6-dependent survival of multiple myeloma cells involves the Stat3-mediated induction of micro-RNA-21 through a highly conserved enhancer
    Ullmann, Kerstin; Stadler, Peter F; Löffler, Dennis; Stocsits, Claudia; Pfeifer, Gabriele; Kretzschmar, Antje K; Cvijic, Helena; Hackermüller, Jörg; Horn, Friedemann; Bauer, Kay; Blumert, Conny; Burger, Renate; Brocke-Heidrich, Katja; Gramatzki, Martin

    Dissertation

    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.

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