Soluble IL6R represents a miR-34a target: Potential implications for the recently identified IL-6R/STAT3/miR-34a feed-back loop

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Abstract

We previously reported that IL-6R, STAT3 and miR-34a form a positive feedbackloop, which promotes epithelial to mesenchymal transition (EMT), invasion, and metastasis of colorectal cancer (CRC) [1]. In that study only the membrane-bound form of the IL-6R was shown to be repressed by miR-34a. Here, we show that also the mRNA encoding the soluble IL6R (s-IL-6R) is directly targeted and repressed by miR-34a. Accordingly, the concentration of s-IL6R protein was decreased in conditioned media of CRC cell lines ectopically expressing miR-34a. The s-IL-6R mediates IL-6 trans-signaling, which also affects cells that do not express the IL-6R. Since IL-6 trans-signaling is involved in numerous inflammatory disease states these findings may be relevant for future therapeutic approaches.

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Li, H., Rokavec, M., & Hermeking, H. (2015). Soluble IL6R represents a miR-34a target: Potential implications for the recently identified IL-6R/STAT3/miR-34a feed-back loop. Oncotarget, 6(16), 14026–14032. https://doi.org/10.18632/oncotarget.4334

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