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

Huihui Li; Matjaz Rokavec; Heiko Hermeking

doi:10.18632/oncotarget.4334

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Priority Research Papers:

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

Huihui Li, Matjaz Rokavec and Heiko Hermeking _

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Oncotarget. 2015; 6:14026-14032. https://doi.org/10.18632/oncotarget.4334

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Abstract

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

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.

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PII: 4334

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Priority Research Papers:

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

Abstract