Article (Scientific journals)
Cytokine-mediated modulation of the hepatic miRNome: miR-146b-5p is an IL-6-inducible miRNA with multiple targets.
Kirchmeyer, Melanie; Servais, Florence; Hamdorf, Matthias et al.
2018In Journal of Leukocyte Biology
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Keywords :
IL-6-type cytokines; hepatocarcinogenesis; liver; miR-146a-5p; microRNAs
Abstract :
[en] Interleukin-6 (IL-6)-type cytokines play important roles in liver (patho-)biology. For instance, they regulate the acute phase response to inflammatory signals and are involved in hepatocarcinogenesis. Much is known about the regulation of protein-coding genes by cytokines whereas their effects on the miRNome is less well understood. We performed a microarray screen to identify microRNAs (miRNAs) in human hepatocytes which are modulated by IL-6-type cytokines. Using samples of 2 donors, 27 and 68 miRNAs (out of 1,733) were found to be differentially expressed upon stimulation with hyper-IL-6 (HIL-6) for up to 72 h, with an overlap of 15 commonly regulated miRNAs. qPCR validation revealed that miR-146b-5p was also consistently up-regulated in hepatocytes derived from 2 other donors. Interestingly, miR-146b-5p (but not miR-146a-5p) was induced by IL-6-type cytokines (HIL-6 and OSM) in non-transformed liver-derived PH5CH8 and THLE2 cells and in Huh-7 hepatoma cells, but not in HepG2 or Hep3B hepatoma cells. We did not find evidence for a differential regulation of miR-146b-5p expression by promoter methylation, also when analyzing the TCGA data set on liver cancer samples. Inducible overexpression of miR-146b-5p in PH5CH8 cells followed by RNA-Seq analysis revealed effects on multiple mRNAs, including those encoding IRAK1 and TRAF6 crucial for Toll-like receptor signaling. Indeed, LPS-mediated signaling was attenuated upon overexpression of miR-146b-5p, suggesting a regulatory loop to modulate inflammatory signaling in hepatocytes. Further validation experiments suggest DNAJC6, MAGEE1, MPHOSPH6, PPP2R1B, SLC10A3, SNRNP27, and TIMM17B to be novel targets for miR-146b-5p (and miR-146a-5p).
Research center :
ULHPC - University of Luxembourg: High Performance Computing
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kirchmeyer, Melanie
Servais, Florence ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Hamdorf, Matthias
Nazarov, Petr V.
Ginolhac, Aurélien  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Halder, Rashi ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Vallar, Laurent
Glanemann, Matthias
Rubie, Claudia
Lammert, Frank
Kreis, Stephanie ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Behrmann, Iris ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
yes
Language :
English
Title :
Cytokine-mediated modulation of the hepatic miRNome: miR-146b-5p is an IL-6-inducible miRNA with multiple targets.
Publication date :
2018
Journal title :
Journal of Leukocyte Biology
ISSN :
0741-5400
Publisher :
Federation of American Societies for Experimental Biology, United States - New York
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Commentary :
(c)2018 The Authors. Society for Leukocyte Biology Published by Wiley Periodicals, Inc.
Available on ORBilu :
since 17 November 2018

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