title: Integrated analysis of mRNA and miRNA expression in response to interleukin-6 in hepatocytes.
abstract: The expression of plasma proteins changes dramatically as a result of cytokine induction, particularly interleukin-6, and their levels are used as clinical markers of inflammation. miRNAs are important regulators of gene expression and play significant roles in many inflammatory diseases and processes. The interactions between miRNAs and the genes that they regulate during the acute phase response have not been investigated. We examined the effects of IL-6 stimulation on the transcriptome and miRNome of human and mouse primary hepatocytes and the HepG2 cell line. Using an integrated analysis, we identified differentially expressed miRNAs whose seed sequences are significantly enriched in the 3' untranslated regions of differentially expressed genes, many of which are involved in inflammation-related pathways. Our finding that certain miRNAs may de-repress critical acute phase proteins within acute timeframes has important biological and clinical implications.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva, Switzerland. Electronic address: samuel.lukowski@unige.ch.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Lukowski
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva, Switzerland.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Fish
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.
authors.forename: Juliette
authors.initials: J
authors.lastname: Martin-Levilain
authors.affiliation: Surgical Research Unit, Department of Surgery, University Hospital, 1211 Geneva, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gonelle-Gispert
authors.affiliation: Surgical Research Unit, Department of Surgery, University Hospital, 1211 Geneva, Switzerland.
authors.forename: Leo H
authors.initials: LH
authors.lastname: Bühler
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Maechler
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva, Switzerland; Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland.
authors.forename: Emmanouil T
authors.initials: ET
authors.lastname: Dermitzakis
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva, Switzerland.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Neerman-Arbez
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000209:Acute-Phase Proteins; D015850:Interleukin-6; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Acute phase response; Hepatocyte; IL-6; Inflammation; Post-transcriptional regulation; Transcriptome; miRNA