Cytokine-mediated modulation of the hepatic miRNome: miR-146b-5p is an IL-6-inducible miRNA with multiple targets

Journal of Leukocyte Biology
Mélanie KirchmeyerIris Behrmann

Abstract

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 fo...Continue Reading

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Citations

Jun 15, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Mireia López-RieraRamiro Jover
Nov 17, 2019·International Journal of Molecular Sciences·Elena PiccininAntonio Moschetta
Apr 3, 2020·PLoS Neglected Tropical Diseases·Hellen Weinschutz MendesIara J Taborda Messias-Reason
Nov 7, 2021·Annals of Neurology·Cindy BokobzaJuliette Van Steenwinckel

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