MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3
Xue Yan,* Dehao Zeng,* He Zhu, Yijing Zhang, Yuying Shi, Yingxiu Wu, Hongmei Tang, Detang Li Pharmaceutical Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, People’s Republic of China*These authors contributed equa...
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Dove Medical Press
2020
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oai:doaj.org-article:60a891a150e24f7e9cc079fc65f344422021-12-02T12:58:08ZMiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT31178-2021https://doaj.org/article/60a891a150e24f7e9cc079fc65f344422020-11-01T00:00:00Zhttps://www.dovepress.com/mirna-532-5p-regulates-cums-induced-depression-like-behaviors-and-modu-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Xue Yan,* Dehao Zeng,* He Zhu, Yijing Zhang, Yuying Shi, Yingxiu Wu, Hongmei Tang, Detang Li Pharmaceutical Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue Yan Tel +86-020-36598864Email zd0171@163.comBackground: It is known that miR-532-5p is critical for neuronal differentiation. However, the role of miR-532-5p in depression remains unknown. This study aimed to investigate the role and mechanism of miR-532-5p in major depressive disorder (MDD).Methods: The depression mice model was established by chronic unpredictable mild stress (CUMS) and confirmed by forced swimming test (FST) and sucrose preference test (SPT). The role of miR-532-5p in MDD was detected by tail suspension test (TST), FST, SPT and SIT. QRT-PCR was used to detect the expression of miR-139-5p in hippocampus and BV-2 microglia of mice. ELISA and Western blotting were used to detect the expression of the nitric oxide synthase (NOS), proinflammatory cytokines (IL-6, IL-1β, TNF-α, and MCP-1) and transcriptional activator 3 (STAT3). Luciferase reporter assay was used to verify the downstream target genes of miR-532-5p.Results: MiR-532-5p was significantly reduced in the hippocampus of mice treated with CUMS. Overexpression of miR-532-5p significantly reduced CUMS-induced depression-like behaviors and suppressed the expression of IL-6, IL-1β, TNF-α and MCP-1. MiR-532-5p directly targeted signal transducers and STAT3 in BV2 cells. In addition, overexpression of miR-532-5p restrained the raise of inducible NOS and IL-6, IL-1 β, TNF-α and MCP-1 in LPS-exposed BV2 cells.Conclusion: This study indicates that miR-532-5p plays an important role in CUMS-induced depression-like behaviors by targeting STAT3, and miR-532-5p may be a potential target for MDD therapy.Keywords: miR-532-5p, STAT3, major depressive disorder, inflammationYan XZeng DZhu HZhang YShi YWu YTang HLi DDove Medical Pressarticlemir-532-5pstat3major depressive disorderinflammationNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 2753-2764 (2020) |
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DOAJ |
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mir-532-5p stat3 major depressive disorder inflammation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
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mir-532-5p stat3 major depressive disorder inflammation Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Yan X Zeng D Zhu H Zhang Y Shi Y Wu Y Tang H Li D MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3 |
| description |
Xue Yan,* Dehao Zeng,* He Zhu, Yijing Zhang, Yuying Shi, Yingxiu Wu, Hongmei Tang, Detang Li Pharmaceutical Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue Yan Tel +86-020-36598864Email zd0171@163.comBackground: It is known that miR-532-5p is critical for neuronal differentiation. However, the role of miR-532-5p in depression remains unknown. This study aimed to investigate the role and mechanism of miR-532-5p in major depressive disorder (MDD).Methods: The depression mice model was established by chronic unpredictable mild stress (CUMS) and confirmed by forced swimming test (FST) and sucrose preference test (SPT). The role of miR-532-5p in MDD was detected by tail suspension test (TST), FST, SPT and SIT. QRT-PCR was used to detect the expression of miR-139-5p in hippocampus and BV-2 microglia of mice. ELISA and Western blotting were used to detect the expression of the nitric oxide synthase (NOS), proinflammatory cytokines (IL-6, IL-1β, TNF-α, and MCP-1) and transcriptional activator 3 (STAT3). Luciferase reporter assay was used to verify the downstream target genes of miR-532-5p.Results: MiR-532-5p was significantly reduced in the hippocampus of mice treated with CUMS. Overexpression of miR-532-5p significantly reduced CUMS-induced depression-like behaviors and suppressed the expression of IL-6, IL-1β, TNF-α and MCP-1. MiR-532-5p directly targeted signal transducers and STAT3 in BV2 cells. In addition, overexpression of miR-532-5p restrained the raise of inducible NOS and IL-6, IL-1 β, TNF-α and MCP-1 in LPS-exposed BV2 cells.Conclusion: This study indicates that miR-532-5p plays an important role in CUMS-induced depression-like behaviors by targeting STAT3, and miR-532-5p may be a potential target for MDD therapy.Keywords: miR-532-5p, STAT3, major depressive disorder, inflammation |
| format |
article |
| author |
Yan X Zeng D Zhu H Zhang Y Shi Y Wu Y Tang H Li D |
| author_facet |
Yan X Zeng D Zhu H Zhang Y Shi Y Wu Y Tang H Li D |
| author_sort |
Yan X |
| title |
MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3 |
| title_short |
MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3 |
| title_full |
MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3 |
| title_fullStr |
MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3 |
| title_full_unstemmed |
MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3 |
| title_sort |
mirna-532-5p regulates cums-induced depression-like behaviors and modulates lps-induced proinflammatory cytokine signaling by targeting stat3 |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/60a891a150e24f7e9cc079fc65f34442 |
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