Up-regulation of microRNA-142 in simian immunodeficiency virus encephalitis leads to repression of sirtuin1
Abstract
MicroRNA (miR)‐142 is up‐regulated in the brain in HIV and SIV encephalitis (SIVE). We identified the cell types where miR‐142 is up‐regulated and its relevant downstream target. Fluorescent in situ hybridization combined with immunofluorescent labeling revealed that miR‐142‐3p and ‐5p are expressed within hippocampal neurons and myeloid cells in SIVE. Sirtuin1 (SIRT1) was predicted as a potential miR‐142 target by analysis of its 3‘‐UTR and bioinformatic analysis of factors linked to altered hippocampal gene expression profile in SIVE. Overexpression of pre‐miR‐142 in HEK293T cells led to a 3.7‐fold decrease in SIRT1 protein level. Examination of the individual effects of miR‐142‐5p and miR‐142‐3p through overexpression and inhibition studies revealed that significant effects on SIRT1 occurred only with miR‐142‐5p. Luciferase reporter assays revealed a 2.3‐fold inhibition of expression due to interaction of miR‐142 with the SIRT1 3‘‐UTR, mutation analysis revealed that only the miR‐142‐5p target site was active. MiR‐142 expression in primary human neurons led to a small (1.3‐fold) but significant decrease in SIRT1 protein level. Furthermore, qRT‐PCR revealed up‐regulation of miR‐142‐3p (6.4‐fold) and ‐5p (3.9‐fold) and down‐regulation of SIRT1 (33‐fold) in macrophages/microglia from animals with SIVE. We have therefore elucidated a miR‐mediated mechanism of regulation of SIRT1 expression in SIVE.—Chaudhuri, A. D., Yelamanchili, S. V., Marcondes, M. C. G., Fox, H. S., Up‐regulation of microRNA‐142 in simian immunodeficiency virus encephalitis leads to repression of sirtuin1. FASEB J. 27, 3720–3729 (2013). www.fasebj.org
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miR-142-3p functions as a regulator of neuroinflammation by modulating expression of proinflammatory mediators in response to different pathological stimuli.
“Several studies have shown that miR-142-3p functions as a regulator of neuroinflammation by modulating the expression of proinflammatory mediators in response to different pathological stimuli, such as multiple sclerosis, neuropathic pain, human immunodeficiency virus (HIV) and simian immunodeficiency virus encephalitis (SIVE; Chaudhuri et al., 2013; Talebi et al., 2017; Zhang et al., 2018).”
From miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A (2020) · cites this paper as Chaudhuri et al., 2013
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- Authors
- Chaudhuri, A. D., Yelamanchili, S. V., Marcondes, M. C. G., & Fox, H. S.
- Affiliations
- Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA
- Department of Molecular and Cellular Neuroscience The Scripps Research Institute La Jolla California USA
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2013-06-10
- Volume
- 27
- Issue
- 9
- Pages
- 3720-3729
- ISSN
- 0892-6638
- 1530-6860
- Cited by
- 67
- References
- 6
- Language
- en
- Funders
- National Institutes of Health (P30 MH062261, R01 MH073490, R21 DA029491)
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