During the last decades, a number of key mediators of inflammation-induced tumorigenesis have been identified to support tumor progression in response to inflammation stimulation1. Recent studies show that a few cancer-related microRNAs (miRNAs) are modulated by inflammation signals2,3, implicating miRNAs as a new class of mediators between inflammation and cancer. However, how inflammation regulates miRNAs in cancer cells and how such miRNA mediators function in inflammation-associated tumorigenesis remain largely unexplored. miRNA-155 (miR-155) has been documented as one of the most prominent miRNAs linking inflammation to cancer4. On one hand, mir-155 is ubiquitously induced by inflammation stimuli3; on the other hand, miR-155 leads to the constitutive activation of pro-tumorigenic inflammatory STAT3 signaling by targeting socs15 and conveys the inflammatory signals to the Warburg effect by upregulating hexokinase-26. We previously observed that pro-inflammatory cytokine interleukin-6 (IL-6)-induced miR-155 represses a specific miRNA gene mir-143 through targeting a transcription factor6; however, it is unclear how generally this mechanism might be utilized in the regulation of miRNAs by inflammation. In the present study, we show that miR-155 acts as a key regulating node linking inflammation to expression control of a number of cancer-related miRNAs, revealing a novel mechanism for the regulation of miRNAs by inflammation.

Given that miR-155 plays a well-evident role in linking inflammation and cancer4, we asked whether miR-155, induced by IL-6 via NF-κB pathway in breast cancer cells6, is involved in the regulation of miRNAs by IL-6. To this end, we used anti-miR-155 to inhibit miR-155 function in IL-6-treated MCF-7 cells (Supplementary information, Figure S1A). Intriguingly, we found that anti-miR-155 completely attenuated the impact of IL-6 on 17 out of the 24 IL-6-affected miRNAs, including 12 IL-6-upregulated miRNAs and 5 IL-6-downregulated miRNAs (Figure 1A), indicating that miR-155 acts as an important mediator in the miRNA regulation by IL-6 in breast cancer cells.

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