Immunology MicroRNA May Link Inflammation and Cancer

L. Bryan Ray

Science, Science’s STKE, AAAS, Washington, DC 20005, USA

For mammals, inflammatory responses of the innate immune system provide an indispensable protective mechanism against infection. But these signaling mechanisms may also contribute to certain diseases, including cancer. O’Connell et al. investigated the role of microRNAs (noncoding RNAs that regulate gene expression through interaction with cellular mRNAs) in the inflammatory response to viral infection and may have unearthed a molecular link between inflammation and cancer. The authors used microarrays to monitor expression of a panel of 200 microRNAs in response to polyriboinosinic:polyribocytidylic acid [poly(I:C)], a synthetic double-stranded RNA used to mimic viral infection, or the antiviral cytokine interferon- (IFN-). They identified one microRNA, miR-155, that showed increased expression in macrophages in response to both stimuli. Expression of miR-155 was regulated through multiple signaling pathways. The response to poly(I:C) required signaling through Toll receptors and the MyD88 or TRIF adaptor proteins. Interferons, on the other hand, stimulated expression of miR-155 through a slower mechanism that required autocrine signals mediated by tumor necrosis factor . Both pathways appeared to converge on regulation of an AP-1 transcription factor binding site, and an inhibitor of the JNK mitogen-activated protein kinase inhibited the response to poly(I:C) or interferon. The miR-155 microRNA is also an oncogene, and its overexpression can cause B cell lymphoma. Thus, the authors note that the finding of miR-155 as a common target of pathways activated by viral infection presents a potential link between inflammatory responses and cancer.

R. M. O’Connell, K. D. Taganov, M. P. Boldin, G. Cheng, D. Baltimore, MicroRNA-155 is induced during the macrophage inflammatory response. Proc. Natl. Acad. Sci. U.S.A. 104, 1604-1609 (2007). [Abstract] [Full Text]

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