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

Sowmya V Yelamanchili, A. Datta Chaudhuri, L. N. Chen, Huangui Xiong, Howard S Fox

Research output: Contribution to journalArticle

66 Citations (Scopus)

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 1 2010

Fingerprint

MEF2 Transcription Factors
Virus Diseases
MicroRNAs
Haplorhini
HIV
Neurons
Simian Immunodeficiency Virus
Encephalitis
Dementia
Physiological Phenomena
Brain
Brain Diseases
N-Methylaspartate
Neurodegenerative Diseases
In Situ Hybridization
Carcinogenesis
Transcription Factors
Down-Regulation
Messenger RNA

Keywords

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

ASJC Scopus subject areas

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

Cite this

MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease. / Yelamanchili, Sowmya V; Datta Chaudhuri, A.; Chen, L. N.; Xiong, Huangui; Fox, Howard S.

In: Cell Death and Disease, Vol. 1, No. 9, e77, 01.09.2010.

Research output: Contribution to journalArticle

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