title: 5-lipoxygenase is a direct target of miR-19a-3p and miR-125b-5p.
abstract: 5-Lipoxygenase (5-LO) is the key enzyme in leukotriene biosynthesis. Leukotrienes are mediators of the innate immune system and inflammatory processes, and they might also be involved in cancer development. MicroRNAs (miRNAs) are important translational regulators and have been shown to be involved in development, differentiation, and cancer. Unraveling the miRNA network is important for understanding the cellular regulation processes. We identified two new miRNAs, miR-19a-3p and miR-125b-5p, regulating 5-LO and confirmed direct interaction by reporter gene assays. Furthermore, we investigated the regulation of 5-LO by these two miRNAs in several cell types. Inhibition of both miRNAs by antagomirs during differentiation of the myeloid cell line Mono Mac 6 led to a significant increase in 5-LO protein expression. Stimulation of human T lymphocytes with PHA resulted in a strong downregulation of 5-LO mRNA expression and in the induction of miR-19a-3p. The inhibition of miR-19a-3p with an antagomir led to a significant increase in 5-LO mRNA expression in T lymphocytes. Taken together, our data reveal that miR-19a-3p and miR-125b-5p target 5-LO in a cell type- and stimulus-specific manner.
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe University, 60438 Frankfurt/Main, Germany;
authors.forename: Saskia
authors.initials: S
authors.lastname: Busch
authors.affiliation: Laboratory for Stem Cell Transplantation and Immunotherapy, Pediatric Hematology and Oncology, University Hospital Frankfurt, 60596 Frankfurt, Germany;
authors.forename: Eileen
authors.initials: E
authors.lastname: Auth
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe University, 60438 Frankfurt/Main, Germany;
authors.forename: Friederike
authors.initials: F
authors.lastname: Scholl
authors.affiliation: Laboratory for Stem Cell Transplantation and Immunotherapy, Pediatric Hematology and Oncology, University Hospital Frankfurt, 60596 Frankfurt, Germany;
authors.forename: Sabine
authors.initials: S
authors.lastname: Huenecke
authors.affiliation: Integrated Research and Treatment Center Transplantation, Institute of Cellular Therapeutics, Hannover Medical School, 30625 Hannover, Germany; and.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
authors.affiliation: Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany steinhilber@em.uni-frankfurt.de bsuess@bio.tu-darmstadt.de.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Suess
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe University, 60438 Frankfurt/Main, Germany; steinhilber@em.uni-frankfurt.de bsuess@bio.tu-darmstadt.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002469:Cell Separation; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D035683:MicroRNAs / Q000276:immunology*; D016297:Mutagenesis, Site-Directed; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C531888:MIRN125 microRNA, human; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D001094:Arachidonate 5-Lipoxygenase