MicroRNA Circuits Regulate the Cancer-Inflammation Link

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Sci. Signal.  25 Mar 2014:
Vol. 7, Issue 318, pp. pe8
DOI: 10.1126/scisignal.2005053

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Genetic and epigenetic perturbations are required to transform normal cells into cancer cells. Inflammatory signaling pathways are activated in various cancers, linking chronic inflammation to oncogenesis. However, the molecular circuits that result in sustained activation of these inflammatory factors are not yet well understood. In the 28 January 2014 issue of Science Signaling, Xiang et al. identified a microRNA-mediated anti-inflammatory circuit that is repressed epigenetically in receptor-negative breast cancers. A high-throughput screen for signal transducer and activator of transcription 3 (STAT3)–regulated microRNAs revealed microRNA miR-146b as a direct STAT3 target in mammary epithelial cells, but DNA methylation in its promoter area suppressed miR-146b expression in cancer cells. Overexpression of miR-146b suppressed nuclear factor κB (NF-κB)–dependent expression of IL6 and subsequent STAT3 activation and decreased the STAT3-induced invasiveness and mesenchymal phenotype of breast cancer cells. Overall, this study contributes to our understanding of how inflammation is involved in oncogenic transformation. Further studies could evaluate the therapeutic potential of targeting this circuit in estrogen receptor–negative breast cancers.

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