title: Soluble IL6R represents a miR-34a target: potential implications for the recently identified IL-6R/STAT3/miR-34a feed-back loop.
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.
authors.affiliation: Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Huihui
authors.initials: H
authors.lastname: Li
authors.affiliation: Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Matjaz
authors.initials: M
authors.lastname: Rokavec
authors.affiliation: Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Hermeking
mesh_terms: D000818:Animals; D001483:Base Sequence; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005246:Feedback; D019073:HT29 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C508603:IL6R protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: IL-6R; STAT3; colorectal cancer; inflammation; miR-34a