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

Cell Death Dis. 2010;1(9):e77. doi: 10.1038/cddis.2010.56.


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.

Keywords: HIV; MEF2C; NMDA; SIV; dementia; monkey; neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Down-Regulation
  • HIV Infections / genetics*
  • HIV Infections / metabolism
  • Haplorhini
  • Humans
  • MEF2 Transcription Factors
  • MicroRNAs / metabolism*
  • Myogenic Regulatory Factors / genetics*
  • Myogenic Regulatory Factors / metabolism
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / virology
  • Neurons / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Simian Acquired Immunodeficiency Syndrome / genetics*
  • Simian Acquired Immunodeficiency Syndrome / metabolism
  • Simian Acquired Immunodeficiency Syndrome / virology


  • MEF2 Transcription Factors
  • MIRN21 microRNA, human
  • MicroRNAs
  • Myogenic Regulatory Factors
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate