title: MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease.
abstract: MicroRNAs (miRNAs) play important roles in regulating a plethora of physiological and pathophysiogical processes including neurodegeneration. In both HIV associated dementia in humans and its monkey model SIV encephalitis we find miR-21, a miRNA largely known for its link to oncogenesis, to be significantly upregulated in the brain. In situ hybridization of the diseased brain sections revealed induction of miR-21 in neurons. MiR-21 can be induced in neurons by prolonged N-methyl-D-aspartic acid receptor stimulation, an excitotoxic process active in HIV and other neurodegenerative diseases. Introduction of miR-21 into human neurons leads to pathological functional defects. Furthermore, we show that miR-21 specifically targets the mRNA of myocyte enhancer factor 2C (MEF2C), a transcription factor crucial for neuronal function, and reduces its expression. MEF2C is dramatically downregulated in neurons of HIV-associated dementia patients as well as monkeys with SIVE. Together, this study elucidates a novel role for miR-21 in the brain, not only as a potential signature of neurological disease but also as a crucial effector of HIV induced neuronal dysfunction and neurodegeneration.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Yelamanchili
authors.forename: A Datta
authors.initials: AD
authors.lastname: Chaudhuri
authors.forename: L-N
authors.initials: LN
authors.lastname: Chen
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
authors.forename: H S
authors.initials: HS
authors.lastname: Fox
mesh_terms: D000818:Animals; D015536:Down-Regulation; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D064326:MEF2 Transcription Factors; D035683:MicroRNAs / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000378:metabolism / Q000821:virology
chemical_list: D064326:MEF2 Transcription Factors; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate