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miRNA-544a Regulates the Inflammation of Spinal Cord Injury by Inhibiting the Expression of NEUROD4

Yang, Lei, Ge, Dawei, Chen, Xi, Jiang, Chunzhi, Zheng, Shengnai·2018·Cellular Physiology and Biochemistry
DOI 10.1159/000495717
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Abstract

Background/Aims: To explore the potential role of miR-544a in spinal cord injury and the possible mechanism involved. Methods: We established a mouse model with spinal cord injury to examine the changes in grip force recovery of the forelimb or the posterior limb of the mouse. Microarray was performed to achieve differentiated miRNAs in the mice. The expressions of miR-544a, MCP-1, IL36B and IL17B after spinal cord injury were detected by qRT-PCR. Subsequently, miR-544a was overexpressed to observe changes in inflammation and grip strength after spinal cord injury. Target gene of miR-544a was then predicted using bioinformatics technology. Finally, dual luciferase reporter gene assay was used to verify the binding of miR-544a to its target gene. Results: Using mice models with spinal cord injury, we found that the strength of their four limbs began to recover 7 days after injury. The results of microarray and qRT-PCR confirmed that mir-544a level in mice with spinal cord injury decreased with increase of injury time, while the levels of inflammatory genes MCP-1 (monocyte chemoattractant protein-1), IL1 (interleukin-1) and TNF-α (tumor necrosis factor alpha) IL36B (interleukin-36 beta) and IL17B (interleukin-17 beta) were significantly increased. However, overexpression of miR-544a in the mice significantly reduced the level of inflammation and restored their grip strength in their four limbs. Finally, we found that miR-544a can bind to the NEUROD4 (Neurogenic differentiation 4) 3’UTR (Untranslated Region) region through bioinformatics website prediction, which was further confirmed by dual luciferase reporter assay. NEUROD4 level was significantly reduced following the overexpression of miR-544a. Conclusion: The expression of miR-544a was significantly decreased after spinal cord injury. High expression of miR-544a could alleviate the inflammation caused by spinal cord injury and promote the recovery of spinal cord via the inhibition of NEUROD4.

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  • Loss of motor neuron-enriched miR-544 in whole spinal cord lysates has been associated with spinal cord injury or amyotrophic lateral sclerosis mutation-carrying muscle.

    “The loss of motor neuron-enriched miR-544 in whole spinal cord lysates has been associated with insults in the form of spinal cord injury29 or amyotrophic lateral sclerosis mutation-carrying muscle30, indicating a novel regulatory mechanism underlying motor neuron homeostasis.”

    From CNS microRNA profiles: a database for cell type enriched microRNA expression across the mouse central nervous system (2020) · cites this paper as [29]

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Research works printed but not linked: 29

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Authors
Yang, L., Ge, D., Chen, X., Jiang, C., & Zheng, S.
Venue
Cellular Physiology and Biochemistry
Publisher
S. Karger AG
Published
2018
Volume
51
Issue
4
Pages
1921-1931
ISSN
  • 1015-8987
  • 1421-9778
DOI
10.1159/000495717
Cited by
34
References
0
Language
en
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