5-lipoxygenase is a direct target of miR-19a-3p and miR-125b-5p

J Immunol. 2015 Feb 15;194(4):1646-53. doi: 10.4049/jimmunol.1402163. Epub 2015 Jan 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / biosynthesis*
  • Arachidonate 5-Lipoxygenase / genetics
  • Blotting, Western
  • COS Cells
  • Cell Line
  • Cell Separation
  • Chlorocebus aethiops
  • Flow Cytometry
  • Gene Expression Regulation / immunology*
  • Humans
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • MicroRNAs / immunology*
  • Mutagenesis, Site-Directed
  • Real-Time Polymerase Chain Reaction

Substances

  • MIRN125 microRNA, human
  • MIRN19 microRNA, human
  • MicroRNAs
  • Arachidonate 5-Lipoxygenase