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

// Huihui Li 1,* , Matjaz Rokavec 1,* and Heiko Hermeking 1,2,3 1 Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universitat Munchen, 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 Correspondence to: Heiko Hermeking, email: // Keywords : miR-34a, colorectal cancer, IL-6R, STAT3, inflammation Received : May 04, 2015 Accepted : May 24, 2015 Published : June 02, 2015 Abstract 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) [ 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.