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MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease
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-2...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002786/ https://www.ncbi.nlm.nih.gov/pubmed/21170291 http://dx.doi.org/10.1038/cddis.2010.56 |
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author | Yelamanchili, S V Chaudhuri, A Datta Chen, L-N Xiong, H Fox, H S |
author_facet | Yelamanchili, S V Chaudhuri, A Datta Chen, L-N Xiong, H Fox, H S |
author_sort | Yelamanchili, S V |
collection | PubMed |
description | 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--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. |
format | Text |
id | pubmed-3002786 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-30027862010-12-16 MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease Yelamanchili, S V Chaudhuri, A Datta Chen, L-N Xiong, H Fox, H S Cell Death Dis Original Article 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--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. Nature Publishing Group 2010-09 2010-09-23 /pmc/articles/PMC3002786/ /pubmed/21170291 http://dx.doi.org/10.1038/cddis.2010.56 Text en Copyright © 2010 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Original Article Yelamanchili, S V Chaudhuri, A Datta Chen, L-N Xiong, H Fox, H S MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease |
title | MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease |
title_full | MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease |
title_fullStr | MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease |
title_full_unstemmed | MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease |
title_short | MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease |
title_sort | microrna-21 dysregulates the expression of mef2c in neurons in monkey and human siv/hiv neurological disease |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002786/ https://www.ncbi.nlm.nih.gov/pubmed/21170291 http://dx.doi.org/10.1038/cddis.2010.56 |
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