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

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 en...

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Bibliographic Details
Published in:Blood 2007-08, Vol.110 (4), p.1330-1333
Main Authors: Löffler, Dennis, Brocke-Heidrich, Katja, Pfeifer, Gabriele, Stocsits, Claudia, Hackermüller, Jörg, Kretzschmar, Antje K., Burger, Renate, Gramatzki, Martin, Blumert, Conny, Bauer, Kay, Cvijic, Helena, Ullmann, A. Kerstin, Stadler, Peter F., Horn, Friedemann
Format: Article
Language:English
Subjects:
Apoptosis
Cell Line, Tumor
Chromatin Immunoprecipitation
Enhancer Elements, Genetic - genetics
Gene Expression Regulation, Neoplastic
Humans
Interleukin-6 - pharmacology
MicroRNAs - physiology
Multiple Myeloma - drug therapy
Multiple Myeloma - genetics
Multiple Myeloma - metabolism
STAT3 Transcription Factor - metabolism
Transcription, Genetic
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2007-03-081133