Figure 3.

STAT3 interacts with other signaling pathways, including NF-κB. Under normal conditions, NF-κB activation can lead to production of the cytokine IL-6, which can then drive STAT3 activation. However, STAT3 induces expression of the microRNA miR-146b, which then attenuates the activation of NF-κB and decreases IL-6 production. This leads to a controlled inflammatory response (A). In cancer cells, the STAT3-induced miR-146b expression does not occur, often through methylation of the miR-146b promoter. This can lead to continued activation of both NF-κB and STAT3, with increased expression of target genes leading to malignant cellular behavior (B).