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 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.
Löffler
Dennis
D
Institute of Clinical Immunology and Transfusion Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany.
Brocke-Heidrich
Katja
K
Pfeifer
Gabriele
G
Stocsits
Claudia
C
Hackermüller
Jörg
J
Kretzschmar
Antje K
AK
Burger
Renate
R
Gramatzki
Martin
M
Blumert
Conny
C
Bauer
Kay
K
Cvijic
Helena
H
Ullmann
A Kerstin
AK
Stadler
Peter F
PF
Horn
Friedemann
F
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
D015850:Interleukin-6; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human