MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3
Open accessAbstract
BACKGROUND: 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.
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Expression of miR-124, miR-532-5p, and miR-9-5p alters in tissues from depression patients or animal models, activating STAT3 and mediating disruption of neuronal differentiation and proliferation in depression.
“the expression of miR-124, miR-532-5p, and miR-9-5p alters in tissues from depression patients/animal models, activating signal transducer and activator of transcription 3 (STAT3) and mediating the disruption of neuronal differentiation and proliferation in depression.259–262”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [260]
The Discussion reports reduced miR-532-5p in the hippocampus of CUMS mice, and the Results show that miR-532-5p targets STAT3 and reduces its expression when overexpressed. The paper does not establish that this pathway disrupts neuronal differentiation or proliferation; it studies inflammatory signaling instead. It also does not provide findings on miR-124 or miR-9-5p. (LLM, conf=0.87)
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- Authors
- Yan, X., Zeng, D., Zhu, H., Zhang, Y., Shi, Y., Wu, Y., Tang, H., & Li, D.
- Affiliations
- First Affiliated Hospital of Guangzhou University of Chinese Medicine (CN)
- Venue
- Neuropsychiatric Disease and Treatment
- Publisher
- Informa UK Limited
- Published
- 2020-11
- Volume
- Volume 16
- Pages
- 2753-2764
- ISSN
- 1176-6328 (ISSN-L)
- 1178-2021
- PMC
- PMC7669525
- OpenAlex
- W3102460079
- Cited by
- 29
- References
- 41
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 10 · 2021: 7
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neuropsychiatric Disease and Treatment (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- Traditional Chinese Medicine Bureau of Guangdong Province
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-532-5p, major depressive disorder, chronic unpredictable mild stress, STAT3, inflammatory cytokines, microglia, lipopolysaccharide, hippocampus, inducible nitric oxide synthase, interleukin-6, IL-1β, TNF-α, MCP-1, depression-like behavior, microRNA therapeutic target
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