Cargando…

Role of circular RNA expression in the pathological progression after spinal cord injury

Differential expression of non-coding RNA after traumatic spinal cord injury (TSCI) is closely related to the pathophysiological process. The purposes of this study were to systematically profile and characterize expression of circular RNA (circRNA) in the lesion epicenter of spinal tissues after TS...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Wen-Zhao, Li, Jun, Liu, Lei, Zhang, Zheng-Dong, Li, Ming-Xin, Li, Qin, Ma, Hui-Xu, Yang, Hai, Hou, Xiao-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343338/
https://www.ncbi.nlm.nih.gov/pubmed/33642393
http://dx.doi.org/10.4103/1673-5374.308100
_version_ 1783734266805354496
author Wang, Wen-Zhao
Li, Jun
Liu, Lei
Zhang, Zheng-Dong
Li, Ming-Xin
Li, Qin
Ma, Hui-Xu
Yang, Hai
Hou, Xiao-Ling
author_facet Wang, Wen-Zhao
Li, Jun
Liu, Lei
Zhang, Zheng-Dong
Li, Ming-Xin
Li, Qin
Ma, Hui-Xu
Yang, Hai
Hou, Xiao-Ling
author_sort Wang, Wen-Zhao
collection PubMed
description Differential expression of non-coding RNA after traumatic spinal cord injury (TSCI) is closely related to the pathophysiological process. The purposes of this study were to systematically profile and characterize expression of circular RNA (circRNA) in the lesion epicenter of spinal tissues after TSCI, and predict the structure and potential function of the regulatory circRNA/miRNA network. Forty-eight C57BL/6 mice were randomly and equally assigned to two groups: one subjected to TSCI at T8–10 with an Allen’s drop impactor, and a second subjected to laminectomy without TSCI. Spinal cord samples were stained with hematoxylin and eosin, sequenced, and validated. RNA-Seq, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and network analyses (Targetscan and miRanda) were used to predict and annotate the circRNA/miRNA/mRNA network. Luciferase reporter, quantitative reverse transcription polymerase chain reaction, and western blot assays were used to profile expression and regulation patterns of the network in mouse models of TSCI. Hematoxylin-eosin staining revealed severe damage to the blood-spinal cord barrier after TSCI. Differentially expressed circRNA and miRNA profiles were obtained after TSCI; differentially expressed circRNAs, which were abundant in the cytoplasm, were involved in positive regulation of transcription and protein phosphorylation. miR-135b-5p was the most significantly downregulated miRNA after TSCI; circRNAAbca1 and KLF4 were predicted to be its target circRNA and mRNA, respectively. Subsequently, the circAbca1/miR-135b-5P/KLF4 regulatory axis was predicted and constructed, and its targeted binding was verified. After inhibiting circAbca1, GAP43 expression was upregulated. Differential expression of circRNAs might play an important role after TSCI. circAbca1 plays a neuroinhibitory role by targeted binding of the miR-135b-5P/KLF4 axis. The identified circRNA/miRNA/mRNA network could provide the basis for understanding pathophysiological mechanisms underlying TSCI, as well as guide the formulation of related therapeutic strategies. All animal protocols were approved by the Research Ethics Committee of West China Hospital of China (approval No. 2017128) on May 16, 2017.
format Online
Article
Text
id pubmed-8343338
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Wolters Kluwer - Medknow
record_format MEDLINE/PubMed
spelling pubmed-83433382021-08-20 Role of circular RNA expression in the pathological progression after spinal cord injury Wang, Wen-Zhao Li, Jun Liu, Lei Zhang, Zheng-Dong Li, Ming-Xin Li, Qin Ma, Hui-Xu Yang, Hai Hou, Xiao-Ling Neural Regen Res Research Article Differential expression of non-coding RNA after traumatic spinal cord injury (TSCI) is closely related to the pathophysiological process. The purposes of this study were to systematically profile and characterize expression of circular RNA (circRNA) in the lesion epicenter of spinal tissues after TSCI, and predict the structure and potential function of the regulatory circRNA/miRNA network. Forty-eight C57BL/6 mice were randomly and equally assigned to two groups: one subjected to TSCI at T8–10 with an Allen’s drop impactor, and a second subjected to laminectomy without TSCI. Spinal cord samples were stained with hematoxylin and eosin, sequenced, and validated. RNA-Seq, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and network analyses (Targetscan and miRanda) were used to predict and annotate the circRNA/miRNA/mRNA network. Luciferase reporter, quantitative reverse transcription polymerase chain reaction, and western blot assays were used to profile expression and regulation patterns of the network in mouse models of TSCI. Hematoxylin-eosin staining revealed severe damage to the blood-spinal cord barrier after TSCI. Differentially expressed circRNA and miRNA profiles were obtained after TSCI; differentially expressed circRNAs, which were abundant in the cytoplasm, were involved in positive regulation of transcription and protein phosphorylation. miR-135b-5p was the most significantly downregulated miRNA after TSCI; circRNAAbca1 and KLF4 were predicted to be its target circRNA and mRNA, respectively. Subsequently, the circAbca1/miR-135b-5P/KLF4 regulatory axis was predicted and constructed, and its targeted binding was verified. After inhibiting circAbca1, GAP43 expression was upregulated. Differential expression of circRNAs might play an important role after TSCI. circAbca1 plays a neuroinhibitory role by targeted binding of the miR-135b-5P/KLF4 axis. The identified circRNA/miRNA/mRNA network could provide the basis for understanding pathophysiological mechanisms underlying TSCI, as well as guide the formulation of related therapeutic strategies. All animal protocols were approved by the Research Ethics Committee of West China Hospital of China (approval No. 2017128) on May 16, 2017. Wolters Kluwer - Medknow 2021-02-19 /pmc/articles/PMC8343338/ /pubmed/33642393 http://dx.doi.org/10.4103/1673-5374.308100 Text en Copyright: © 2021 Neural Regeneration Research https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Research Article
Wang, Wen-Zhao
Li, Jun
Liu, Lei
Zhang, Zheng-Dong
Li, Ming-Xin
Li, Qin
Ma, Hui-Xu
Yang, Hai
Hou, Xiao-Ling
Role of circular RNA expression in the pathological progression after spinal cord injury
title Role of circular RNA expression in the pathological progression after spinal cord injury
title_full Role of circular RNA expression in the pathological progression after spinal cord injury
title_fullStr Role of circular RNA expression in the pathological progression after spinal cord injury
title_full_unstemmed Role of circular RNA expression in the pathological progression after spinal cord injury
title_short Role of circular RNA expression in the pathological progression after spinal cord injury
title_sort role of circular rna expression in the pathological progression after spinal cord injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343338/
https://www.ncbi.nlm.nih.gov/pubmed/33642393
http://dx.doi.org/10.4103/1673-5374.308100
work_keys_str_mv AT wangwenzhao roleofcircularrnaexpressioninthepathologicalprogressionafterspinalcordinjury
AT lijun roleofcircularrnaexpressioninthepathologicalprogressionafterspinalcordinjury
AT liulei roleofcircularrnaexpressioninthepathologicalprogressionafterspinalcordinjury
AT zhangzhengdong roleofcircularrnaexpressioninthepathologicalprogressionafterspinalcordinjury
AT limingxin roleofcircularrnaexpressioninthepathologicalprogressionafterspinalcordinjury
AT liqin roleofcircularrnaexpressioninthepathologicalprogressionafterspinalcordinjury
AT mahuixu roleofcircularrnaexpressioninthepathologicalprogressionafterspinalcordinjury
AT yanghai roleofcircularrnaexpressioninthepathologicalprogressionafterspinalcordinjury
AT houxiaoling roleofcircularrnaexpressioninthepathologicalprogressionafterspinalcordinjury