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Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84

Spinal cord injury (SCI) is a traumatic disease resulting in neuronal injury. circRNAs are closely associated with human diseases. Nevertheless, the potential mechanism by which circRNAs impact SCI remains to be elucidated. The aim of this study was to investigate the regulatory roles of Circular RN...

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Autores principales: Tong, Dake, Zhao, Yanyin, Tang, Yang, Ma, Jie, Wang, Zhiwei, Li, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809980/
https://www.ncbi.nlm.nih.gov/pubmed/34753388
http://dx.doi.org/10.1080/21655979.2021.2004362
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author Tong, Dake
Zhao, Yanyin
Tang, Yang
Ma, Jie
Wang, Zhiwei
Li, Cheng
author_facet Tong, Dake
Zhao, Yanyin
Tang, Yang
Ma, Jie
Wang, Zhiwei
Li, Cheng
author_sort Tong, Dake
collection PubMed
description Spinal cord injury (SCI) is a traumatic disease resulting in neuronal injury. circRNAs are closely associated with human diseases. Nevertheless, the potential mechanism by which circRNAs impact SCI remains to be elucidated. The aim of this study was to investigate the regulatory roles of Circular RNAs (circRNAs) in SCI. The SCI mouse model and integrated bioinformatics analysis were used to identify the differentially expressed genes (DEGs). Functional enrichment analysis was conducted to study the related pathways. The circRNA-mediated ceRNA network and subnetwork was constructed based on circMir, TargetScan and miRanda. qRT–PCR, ELISA, flow cytometry, and luciferase reporter assays were carried out to validate the role of circ_0014637 (circ-Usp10) and microRNA(miR)-152-5p /CD84 in microglia. In all, 23 DE-circRNAs, 127 DE-miRNAs and 1327 DE-mRNAs were identified. We integrated these DEGs to construct a circRNA-miRNA-mRNA network. The circ-Usp10/miR-152-5p/CD84 axis was found to function in microglial activation. We also found that circ-Usp10 inhibited the secretion of proinflammatory factors in microglial BV2 cells. In addition, silencing circ-Usp10 significantly reduced the death of the neuronal cell line HT22. Taken together, we concluded that circ-Usp10 may function as a competing endogenous RNA (ceRNA) to promote microglial activation and induce neuronal death by targeting miR-152-5p/CD84. The circ-Usp10 may be a diagnostic biomarker and potential target for SCI therapy.
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spelling pubmed-88099802022-02-03 Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84 Tong, Dake Zhao, Yanyin Tang, Yang Ma, Jie Wang, Zhiwei Li, Cheng Bioengineered Research Paper Spinal cord injury (SCI) is a traumatic disease resulting in neuronal injury. circRNAs are closely associated with human diseases. Nevertheless, the potential mechanism by which circRNAs impact SCI remains to be elucidated. The aim of this study was to investigate the regulatory roles of Circular RNAs (circRNAs) in SCI. The SCI mouse model and integrated bioinformatics analysis were used to identify the differentially expressed genes (DEGs). Functional enrichment analysis was conducted to study the related pathways. The circRNA-mediated ceRNA network and subnetwork was constructed based on circMir, TargetScan and miRanda. qRT–PCR, ELISA, flow cytometry, and luciferase reporter assays were carried out to validate the role of circ_0014637 (circ-Usp10) and microRNA(miR)-152-5p /CD84 in microglia. In all, 23 DE-circRNAs, 127 DE-miRNAs and 1327 DE-mRNAs were identified. We integrated these DEGs to construct a circRNA-miRNA-mRNA network. The circ-Usp10/miR-152-5p/CD84 axis was found to function in microglial activation. We also found that circ-Usp10 inhibited the secretion of proinflammatory factors in microglial BV2 cells. In addition, silencing circ-Usp10 significantly reduced the death of the neuronal cell line HT22. Taken together, we concluded that circ-Usp10 may function as a competing endogenous RNA (ceRNA) to promote microglial activation and induce neuronal death by targeting miR-152-5p/CD84. The circ-Usp10 may be a diagnostic biomarker and potential target for SCI therapy. Taylor & Francis 2021-12-07 /pmc/articles/PMC8809980/ /pubmed/34753388 http://dx.doi.org/10.1080/21655979.2021.2004362 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Tong, Dake
Zhao, Yanyin
Tang, Yang
Ma, Jie
Wang, Zhiwei
Li, Cheng
Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84
title Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84
title_full Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84
title_fullStr Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84
title_full_unstemmed Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84
title_short Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84
title_sort circ-usp10 promotes microglial activation and induces neuronal death by targeting mirna-152-5p/cd84
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809980/
https://www.ncbi.nlm.nih.gov/pubmed/34753388
http://dx.doi.org/10.1080/21655979.2021.2004362
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