title: Regulation of TREM2 expression by an NF-кB-sensitive miRNA-34a.
abstract: Genetic deficits and loss of function for the triggering receptor expressed in myeloid cells 2 (TREM2; encoded at chr6p21.1), a transmembrane spanning stimulatory receptor of the immunoglobulin/lectin-like gene superfamily, have been associated with deficiencies in phagocytosis and the innate immune system in Alzheimer's disease. In this study, we provide evidence that TREM2 is downregulated in samples of sporadic Alzheimer hippocampal CA1 compared with age-matched controls. A nuclear factor-кB (NF-кB)-sensitive miRNA-34a (encoded at chr1p36.22), upregulated in Alzheimer's disease, was found to target the 299 nucleotide human TREM2 mRNA 3'-untranslated region (3'-UTR) and downregulate the expression of a TREM2-3'-UTR reporter vector. A stabilized anti-miRNA-34a (AM-34a) quenched this pathogenic response. The results suggest that an epigenetic mechanism involving an NF-кB-mediated, miRNA-34a-regulated downregulation of TREM2 expression may shape innate immune and phagocytic responses that contribute to inflammatory neurodegeneration.
authors: Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112-2272, USA.
authors: Yuhai
authors: Y
authors: Zhao
authors: Surjyadipta
authors: S
authors: Bhattacharjee
authors: Brandon M
authors: BM
authors: Jones
authors: Prerna
authors: P
authors: Dua
authors: Peter N
authors: PN
authors: Alexandrov
authors: James M
authors: JM
authors: Hill
authors: Walter J
authors: WJ
authors: Lukiw
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D003627:Data Interpretation, Statistical; D015536:Down-Regulation / Q000187:drug effects; D044127:Epigenesis, Genetic; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology; D011786:Quality Control; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C551848:MIRN34a microRNA, mouse; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D016328:NF-kappa B; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse