CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR‐340‐5p/Smurf1 axis

BACKGROUND: Spinal cord injury (SCI) is a traumatic central nervous system disorder that leads to irreversible neurological dysfunction. Emerging evidence has shown that differentially expressed circular RNAs (circRNAs) after SCI is closely associated with the pathophysiological process. Herein, the...

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Autores principales: Han, Ziyin, Mou, Zufang, Jing, Yulong, Jiang, Rong, Sun, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091371/
https://www.ncbi.nlm.nih.gov/pubmed/37102659
http://dx.doi.org/10.1002/iid3.824
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author Han, Ziyin
Mou, Zufang
Jing, Yulong
Jiang, Rong
Sun, Tao
author_facet Han, Ziyin
Mou, Zufang
Jing, Yulong
Jiang, Rong
Sun, Tao
author_sort Han, Ziyin
collection PubMed
description BACKGROUND: Spinal cord injury (SCI) is a traumatic central nervous system disorder that leads to irreversible neurological dysfunction. Emerging evidence has shown that differentially expressed circular RNAs (circRNAs) after SCI is closely associated with the pathophysiological process. Herein, the potential function of circRNA spermine oxidase (circSmox) in functional recovery after SCI was investigated. METHODS: Differentiated PC12 cells stimulated with lipopolysaccharide (LPS) were employed as an in vitro model for neurotoxicity research. Levels of genes and proteins were detected by quantitative real‐time PCR and Western blot analysis. Cell viability and apoptosis were determined by CCK‐8 assay and flow cytometry. Western blot analysis was used to detect the protein level of apoptosis‐related markers. The levels of interleukin (IL)‐1β, IL‐6, IL‐8, and tumor necrosis factor (TNF)‐α. Dual‐luciferase reporter, RIP, and pull‐down assays were used to confirm the target relationship between miR‐340‐5p and circSmox or Smurf1 (SMAD Specific E3 Ubiquitin Protein Ligase 1). RESULTS: LPS elevated the levels of circSmox and Smurf1, but decreased the levels of miR‐340‐5p in PC12 cells in a dose‐dependent manner. Functionally, circSmox silencing alleviated LPS‐induced apoptosis and inflammation in PC12 cells in vitro. Mechanistically, circSmox directly sponged miR‐340‐5p, which targeted Smurf1. Rescue experiments showed that miR‐340‐5p inhibition attenuated the neuroprotective effect of circSmox siRNA in PC12 cells. Moreover, miR‐340‐5p suppressed LPS‐triggered neurotoxicity in PC12 cells, which was reversed by Smurf1 overexpression. CONCLUSION: CircSmox enhances LPS‐induced apoptosis and inflammation via miR‐340‐5p/Smurf1 axis, providing an exciting view of the potential involvement of circSmox in SCI pathogenesis.
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spelling pubmed-100913712023-04-13 CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR‐340‐5p/Smurf1 axis Han, Ziyin Mou, Zufang Jing, Yulong Jiang, Rong Sun, Tao Immun Inflamm Dis Original Articles BACKGROUND: Spinal cord injury (SCI) is a traumatic central nervous system disorder that leads to irreversible neurological dysfunction. Emerging evidence has shown that differentially expressed circular RNAs (circRNAs) after SCI is closely associated with the pathophysiological process. Herein, the potential function of circRNA spermine oxidase (circSmox) in functional recovery after SCI was investigated. METHODS: Differentiated PC12 cells stimulated with lipopolysaccharide (LPS) were employed as an in vitro model for neurotoxicity research. Levels of genes and proteins were detected by quantitative real‐time PCR and Western blot analysis. Cell viability and apoptosis were determined by CCK‐8 assay and flow cytometry. Western blot analysis was used to detect the protein level of apoptosis‐related markers. The levels of interleukin (IL)‐1β, IL‐6, IL‐8, and tumor necrosis factor (TNF)‐α. Dual‐luciferase reporter, RIP, and pull‐down assays were used to confirm the target relationship between miR‐340‐5p and circSmox or Smurf1 (SMAD Specific E3 Ubiquitin Protein Ligase 1). RESULTS: LPS elevated the levels of circSmox and Smurf1, but decreased the levels of miR‐340‐5p in PC12 cells in a dose‐dependent manner. Functionally, circSmox silencing alleviated LPS‐induced apoptosis and inflammation in PC12 cells in vitro. Mechanistically, circSmox directly sponged miR‐340‐5p, which targeted Smurf1. Rescue experiments showed that miR‐340‐5p inhibition attenuated the neuroprotective effect of circSmox siRNA in PC12 cells. Moreover, miR‐340‐5p suppressed LPS‐triggered neurotoxicity in PC12 cells, which was reversed by Smurf1 overexpression. CONCLUSION: CircSmox enhances LPS‐induced apoptosis and inflammation via miR‐340‐5p/Smurf1 axis, providing an exciting view of the potential involvement of circSmox in SCI pathogenesis. John Wiley and Sons Inc. 2023-04-12 /pmc/articles/PMC10091371/ /pubmed/37102659 http://dx.doi.org/10.1002/iid3.824 Text en © 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Han, Ziyin
Mou, Zufang
Jing, Yulong
Jiang, Rong
Sun, Tao
CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR‐340‐5p/Smurf1 axis
title CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR‐340‐5p/Smurf1 axis
title_full CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR‐340‐5p/Smurf1 axis
title_fullStr CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR‐340‐5p/Smurf1 axis
title_full_unstemmed CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR‐340‐5p/Smurf1 axis
title_short CircSmox knockdown alleviates PC12 cell apoptosis and inflammation in spinal cord injury by miR‐340‐5p/Smurf1 axis
title_sort circsmox knockdown alleviates pc12 cell apoptosis and inflammation in spinal cord injury by mir‐340‐5p/smurf1 axis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091371/
https://www.ncbi.nlm.nih.gov/pubmed/37102659
http://dx.doi.org/10.1002/iid3.824
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