MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease

S. V. Yelamanchili, A. Datta Chaudhuri, L. N. Chen, H. Xiong, H. S. Fox

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

MicroRNAs (miRNAs) have important roles in regulating a plethora of physiological and pathophysiogical processes including neurodegeneration. In both human immunodeficiency virus (HIV)-associated dementia in humans and its monkey model simian immunodeficiency virus encephalitis (SIVE), 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.

Original languageEnglish (US)
Article numbere77
JournalCell Death and Disease
Volume1
Issue number9
DOIs
StatePublished - Sep 2010

Keywords

  • Dementia
  • HIV
  • MEF2C
  • Monkey
  • NMDA
  • Neurodegeneration
  • SIV

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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