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Sci. Signal., 28 January 2014
Vol. 7, Issue 310, p. ra11
[DOI: 10.1126/scisignal.2004497]

RESEARCH ARTICLES

Editor's Summary

Micro-Mediated Feedback
Chronic inflammation and interleukin-6 (IL-6), which is produced in response to nuclear factor {kappa}B (NF-{kappa}B) signaling, is a proinflammatory cytokine associated with cancer. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor stimulated in response to IL-6 and its receptor-bound kinases from the Janus kinase (JAK) family. Xiang et al. found that STAT3 stimulated expression of the gene encoding the microRNA miR-146b, which inhibited NF-{kappa}B–mediated induction of IL-6 to prevent a proinflammatory response in normal breast epithelial cells. However, promoter methylation reduced miR-146b expression in breast cancer cell lines and patient tissue, and its expression correlated with survival in patients with estrogen receptor– or triple-negative breast cancer. In addition to inhibiting STAT3 activity and cell migration and invasion, introduction of a miR-146b mimic was as cytotoxic as pharmacological inhibition of JAK to triple-negative breast cancer cells in culture, and combination therapy in cells was additive. The findings suggest that therapies reintroducing or stimulating miR-146b production may be beneficial to patients with tumors with high STAT3 activity.

Citation: M. Xiang, N. J. Birkbak, V. Vafaizadeh, S. R. Walker, J. E. Yeh, S. Liu, Y. Kroll, M. Boldin, K. Taganov, B. Groner, A. L. Richardson, D. A. Frank, STAT3 Induction of miR-146b Forms a Feedback Loop to Inhibit the NF-{kappa}B to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes. Sci. Signal. 7, ra11 (2014).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
MicroRNA Circuits Regulate the Cancer-Inflammation Link.
D. Iliopoulos (2014)
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