Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 May 10:12:125.
doi: 10.3389/fnmol.2019.00125. eCollection 2019.

MicroRNAs in Microglia: How do MicroRNAs Affect Activation, Inflammation, Polarization of Microglia and Mediate the Interaction Between Microglia and Glioma?

Yawei Guo  1 , Wenming Hong  1   2 , Xinming Wang  1 , Pengying Zhang  1 , Heinrich Körner  1 , Jiajie Tu  1 , Wei Wei  1
Affiliations
Review

MicroRNAs in Microglia: How do MicroRNAs Affect Activation, Inflammation, Polarization of Microglia and Mediate the Interaction Between Microglia and Glioma?

Yawei Guo et al. Front Mol Neurosci. .

Abstract

The essential roles of microglia in maintaining homeostasis in the healthy brain and contributing to neuropathology are well documented. Emerging evidence suggests that epigenetic modulation regulates microglial behavior in both physiological and pathological conditions. MicroRNAs (miRNAs) are short, non-coding epigenetic regulators that repress target gene expression mostly via binding to 3'-untranslated region (3'-UTR) of mRNA in a Dicer-dependent manner. Dysregulation of certain miRNAs can contribute to microglial hyper-activation, persistent neuroinflammation, and abnormal macrophage polarization in the brain. These abnormal conditions can support the pathogenesis of neurological disorders such as glioma, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), stroke, ischemia, and spinal cord injury (SCI). However, the roles of miRNAs in microglia in health and neurological disease have not been systematically summarized. This review will first report the role of Dicer, a key endoribonulease that is responsible for most miRNA biogenesis in microglia. Second, we will focus on recent research about the function of miRNAs in activation, inflammation and polarization of microglia, respectively. In addition, potential crosstalk between microglia and glioma cells via miRNAs will be discussed in this part. Finally, the role of two essential miRNAs, miR-124, and miR-155, in microglia will be highlighted.

Keywords: activation; glioma; inflammation; microRNA; microglia; polarization.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The role of Dicer in embryonic and adult microglia. Ablation of Dicer in microglia during embryonic development leads to spontaneous microglial activation and impaired genome integrity. A conditional Dicer knockout in microglia shows hyper-activation upon stimulation in adult mice. Additionally, Dicer-deletion microglia show increased sensitivity to irradiation in both embryonic and adult stages.
Figure 2
Figure 2
The relationship between microRNAs (miRNAs) and NF-κB pathway in microglia. Among microglia activation-related miRNAs, the direct targets of most miRNAs (miR-27a, miR-181c, miR-203, miR-125b, miR-199, miR-29b, miR-7 and miR-146a) are within NF-κB pathway.
Figure 3
Figure 3
The effects of miRNA on microglial polarization. miR-128 and miR-124 could promote and repress M1 and M2 polarization of microglia, respectively.
Figure 4
Figure 4
MicroRNA-mediated interactions between microglia and glioma. (A) miR-219-5p, miR-219-2-3p, and miR-338-3p were identified as the top three miRNAs in the tumor border and miR-376c-3p was reduced in tumor samples, all were closely associated with macrophages/microglia. (B) miR-451, miR-21 and miR-146a in glioma-EVs were found to be transferred to microglia.
Figure 5
Figure 5
The role of miR-124 in microglia. Cocaine, D-4F, Morphine and Laquinimod induce miR-124 expression in microglia. miR-124 affects many cellular function of microglia, including motility, phagocytosis, polarization, differentiation and quiescent state.
Figure 6
Figure 6
The role of miR-155 in microglia. Lipopolysaccharide (LPS)/TLR4 and C-Jun are two upstream regulators of miR-155 in microglia and MAPK/NF-κB/mTOR are downstream pathways of miR-155 in microglia. In addition, miR-155 also affects microglial activation, proliferation, inflammation, differentiation and fuction of other cells in brain (ectopic localization of radial-glia-like cells, astrocyte density and brain endothelial hyperplasia) by directly targeting various genes, including CCN1, RACK, SHIP, SOCS1, RHOA and CCN1.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ajmone-Cat M. A., Bernardo A., Greco A., Minghetti L. (2010). Non-steroidal anti-inflammatory drugs and brain inflammation: effects on microglial functions. Pharmaceuticals 3, 1949–1964. 10.3390/ph3061949 - DOI - PMC - PubMed
    1. Åkerblom M., Sachdeva R., Quintino L., Wettergren E. E., Chapman K. Z., Manfre G., et al. . (2013). Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9. Nat. Commun. 4:1770. 10.1038/ncomms2801 - DOI - PubMed
    1. Amici S. A., Dong J., Guerau-de-Arellano M. (2017). Molecular mechanisms modulating the phenotype of macrophages and microglia. Front. Immunol. 8:1520. 10.3389/fimmu.2017.01520 - DOI - PMC - PubMed
    1. Belarbi K., Tweedie D., Arellano C., Jopson T., Greig N., Rosi S. (2011). Inhibition of TNF-α protein synthesis restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation. Alzheimers Dement. 7:S649 10.1016/j.jalz.2011.05.1861 - DOI - PMC - PubMed
    1. Belter A., Rolle K., Piwecka M., Fedoruk-wyszomirska A., Naskrşt-barciszewska M. Z., Barciszewski J. (2016). Inhibition of miR-21 in glioma cells using catalytic nucleic acids. Sci. Rep. 6:24516. 10.1038/srep24516 - DOI - PMC - PubMed