Priority Research Papers:
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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Huihui Li1,*, Matjaz Rokavec1,* and Heiko Hermeking1,2,3
1 Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany
2 German Cancer Consortium (DKTK), Heidelberg, Germany
3 German Cancer Research Center (DKFZ), Heidelberg, Germany
* These authors have contributed equally to this work
Heiko Hermeking, email:
Keywords: miR-34a, colorectal cancer, IL-6R, STAT3, inflammation
Received: May 04, 2015 Accepted: May 24, 2015 Published: June 02, 2015
We previously reported that IL-6R, STAT3 and miR-34a form a positive feedback-loop, which promotes epithelial to mesenchymal transition (EMT), invasion, and metastasis of colorectal cancer (CRC) . 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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