Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer - PubMed (original) (raw)

. 2007 Aug 15;110(4):1330-3.

doi: 10.1182/blood-2007-03-081133. Epub 2007 May 11.

Katja Brocke-Heidrich, Gabriele Pfeifer, Claudia Stocsits, Jörg Hackermüller, Antje K Kretzschmar, Renate Burger, Martin Gramatzki, Conny Blumert, Kay Bauer, Helena Cvijic, A Kerstin Ullmann, Peter F Stadler, Friedemann Horn

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Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer

Dennis Löffler et al. Blood. 2007.

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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.

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