ID: 194: Role of microRNAs in signal transduction pathways of the inflammatory cytokine Interleukin-6: Relevance for liver diseases

详细信息    查看全文

• 作者：Florence Anne Servais¹ ; ; Mé ; lanie Kirchmeyer¹ ; Matthias Hamdorf¹ ; Claude Haan¹ ; Markus Casper² ; Frank Lammert² ; Petr Nazarov³ ; Laurent Vallar³ ; Stephanie Kreis¹ ; Iris Behrmann¹
• 刊名：Cytokine
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：76
• 期：1
• 页码：99
• 全文大小：46 K

文摘

IL-6 plays important roles in regulation of liver functions and promotes hepatocarcinogenesis. As the contribution of IL-6-induced miRNAs to these effects is largely unknown, we investigate the effects of IL-6 on the miRNome of hepatoma cells and non-transformed hepatocytes. Moreover, little is known about miRNAs regulating key players of IL-6 signal transduction. Therefore, our aims were to identify such miRNAs in a miRNA mimics screen and to elucidate their effects on this pathway. Integration of the results of both approaches is expected to lead to the identification of regulatory circuits.

While IL-6 (and hyperIL-6) induce the differential regulation of thousands of mRNAs in HepG2 and HuH-7 hepatoma cell lines, only selected miRNAs change their expression level significantly, including miR-21, miR-100, miR-145, miR-146b-5p. In contrast, we have observed previously that IFN-g has a profound effect on the miRNome of melanoma cells (Schmitt, Cell Comm. Sign. 2012). Therefore we investigate whether IL-6-type cytokines may have generally weaker effects on the miRNome compared to interferons and/or whether our observation is due to cell type-specific differences.

To extend our in vitro findings, we analyse and correlate the expression levels of miRNAs and inflammatory cytokines in patients with HCC and advanced nonalcoholic steatohepatitis (NASH), the latter being at high risk to develop HCC. Bio-Plex cytokine immunoassays revealed that the serum level of IL-6 and HGF is higher in HCC patients than in healthy controls and NASH patients. Our work may contribute to the identification of novel biomarkers for the progression of chronic liver diseases.