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Cited by 637Cytokine Signaling Pathways and InteractionsMultiple Myeloma Research and TreatmentsMicroRNA in disease regulation

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

Open access
Löffler, Dennis, Brocke-Heidrich, Katja, Pfeifer, Gabriele, Stocsits, Claudia, Hackermüller, Jörg, Kretzschmar, Antje K., Burger, Renate, Gramatzki, Martin +6 more·2007·Blood
DOI 10.1182/blood-2007-03-081133
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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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  • The miR-21 gene contains two conserved STAT3 binding sites within its enhancer region and is induced by interleukin 6 in a STAT3-dependent way.

    “The miR-21 gene contains two conserved STAT3 binding sites within its enhancer region and is induced by interleukin 6 (IL-6) in a STAT3-dependent way.”

    From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [39]

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Research works printed but not linked: 23

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  2. Bromberg JF, Wrzeszczynska MH, Devgan G, et al. Stat3 as an oncogene. Cell. 1999;98:295- 303.
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  18. Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors de- fines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257-2261.
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Authors
Löffler, D., Brocke-Heidrich, K., Pfeifer, G., Stocsits, C., Hackermüller, J., Kretzschmar, A. K., Burger, R., Gramatzki, M., Blumert, C., Bauer, K., Cvijic, H., Ullmann, A. K., Stadler, P. F., & Horn, F.
Affiliations
  • Leipzig University (DE)
  • Fraunhofer Institute for Cell Therapy and Immunology (DE)
  • University Hospital Schleswig-Holstein (DE)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2007-08-15
Volume
110
Issue
4
Pages
1330-1333
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2007-03-081133
OpenAlex
W2010180766
Cited by
637
References
2
Citations by year
2026: 4 · 2025: 7 · 2024: 15 · 2023: 15 · 2022: 18 · 2021: 33 · 2020: 29 · 2019: 28 · 2018: 32 · 2017: 27 · 2016: 36 · 2015: 48 · 2014: 46 · 2013: 48 · 2012: 54
FWCI
23.38
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
  • Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion)
  • Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
  • Qucosa (Saxon State and University Library Dresden) (submittedVersion, other-oa)
Funders
Deutsche Forschungsgemeinschaft (SFB 610, Project C2)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
multiple myeloma, interleukin-6, STAT3, miR-21, enhancers, STAT3 binding sites, gene expression regulation, apoptosis, oncogenic microRNA
MeSH terms
Enhancer Elements, Genetic, Humans, Multiple Myeloma, Transcription, Genetic, Interleukin-6, Gene Expression Regulation, Neoplastic, Apoptosis, MicroRNAs, Cell Line, Tumor, Chromatin Immunoprecipitation, STAT3 Transcription Factor

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