miR-203, fine-tunning neuroinflammation by juggling different components of NF‐κB signaling
Abstract Background miR-203 was first indicated in maintaining skin homeostasis and innate immunity. Aberrant expression of miR-203 was found associated with pathological progressions of immune disorders, cancers, as well as neurodegenerations. Recently, increasing data on miR-203 in regulating neur...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02451-9 |
| _version_ | 1828378854939426816 |
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| author | Shufang Li Linpeng Li Jieli Li Xiaosheng Liang Chao Song Yi Zou |
| author_facet | Shufang Li Linpeng Li Jieli Li Xiaosheng Liang Chao Song Yi Zou |
| author_sort | Shufang Li |
| collection | DOAJ |
| description | Abstract Background miR-203 was first indicated in maintaining skin homeostasis and innate immunity. Aberrant expression of miR-203 was found associated with pathological progressions of immune disorders, cancers, as well as neurodegenerations. Recently, increasing data on miR-203 in regulating neuroinflammation and neuronal apoptosis has raised extensive concern about the biological function of this microRNA. Methods Mouse model with ectopic miR-203 expression in the hippocampus was constructed by stereotactic injection of lentiviral expression vector of pre-miR-203. Association of miR-203 and mRNA of Akirin2, as well as the competition for miR-203 targeting between Akirin2 3ʹUTR and another recently characterized miR-203 target, 14-3-3θ, was verified using Dual-Luciferase Reporter Gene Assay and western blot. Microglia activation and pro-inflammatory cytokines expression in the hippocampus of mice overexpressing miR-203 was evaluated using immunohistochemistry analysis and western blot. Neuronal cell death was monitored using anti-caspase 8 in immunohistochemistry as well as TUNEL assay. Cognition of mice was assessed with a behavior test battery consisting of nesting behavior test, Barnes maze and fear conditioning test. Results Akirin2, an activator of NF‐κB signaling, was identified as a direct target of miR-203. By also targeting 14-3-3θ, a negative regulator of NF‐κB signaling, miR-203 displayed an overall pro-inflammatory role both in vitro and in vivo. Promoted nuclear translocation of NF‐κB and increased expression of proinflammatory cytokines were observed in cultured BV2 cells transfected with miR-203 mimics. Microglia activation and upregulation of NF‐κB, IL-1β and IL-6 were observed in mouse hippocampus with overexpression of miR-203. In addition, promoted neuronal cell death in the hippocampus and impaired neuronal activities resulted in cognitive dysfunction of mice with ectopic miR-203 expression in the hippocampus. Conclusion A pro-inflammatory and neurodisruptive role of miR-203 was addressed based on our data in this study. Given the identification of Akirin2 as a direct target of miR-203 and the competition with 14-3-3θ for miR-203 targeting, together with the findings of other signaling molecules in NF‐κB pathway as targets of miR-203, we proposed that miR-203 was a master modulator, fine-tunning neuroinflammation by juggling different components of NF‐κB signaling. |
| first_indexed | 2024-12-10T03:30:22Z |
| format | Article |
| id | doaj.art-a67f64a02060494fae1e669726538301 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-10T03:30:22Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-a67f64a02060494fae1e6697265383012022-12-22T02:03:50ZengBMCJournal of Neuroinflammation1742-20942022-04-0119111610.1186/s12974-022-02451-9miR-203, fine-tunning neuroinflammation by juggling different components of NF‐κB signalingShufang Li0Linpeng Li1Jieli Li2Xiaosheng Liang3Chao Song4Yi Zou5The Key Laboratory of Virology of Guangzhou, Jinan UniversityThe Key Laboratory of Virology of Guangzhou, Jinan UniversityThe Key Laboratory of Virology of Guangzhou, Jinan UniversityThe Key Laboratory of Virology of Guangzhou, Jinan UniversityThe Key Laboratory of Virology of Guangzhou, Jinan UniversityThe Key Laboratory of Virology of Guangzhou, Jinan UniversityAbstract Background miR-203 was first indicated in maintaining skin homeostasis and innate immunity. Aberrant expression of miR-203 was found associated with pathological progressions of immune disorders, cancers, as well as neurodegenerations. Recently, increasing data on miR-203 in regulating neuroinflammation and neuronal apoptosis has raised extensive concern about the biological function of this microRNA. Methods Mouse model with ectopic miR-203 expression in the hippocampus was constructed by stereotactic injection of lentiviral expression vector of pre-miR-203. Association of miR-203 and mRNA of Akirin2, as well as the competition for miR-203 targeting between Akirin2 3ʹUTR and another recently characterized miR-203 target, 14-3-3θ, was verified using Dual-Luciferase Reporter Gene Assay and western blot. Microglia activation and pro-inflammatory cytokines expression in the hippocampus of mice overexpressing miR-203 was evaluated using immunohistochemistry analysis and western blot. Neuronal cell death was monitored using anti-caspase 8 in immunohistochemistry as well as TUNEL assay. Cognition of mice was assessed with a behavior test battery consisting of nesting behavior test, Barnes maze and fear conditioning test. Results Akirin2, an activator of NF‐κB signaling, was identified as a direct target of miR-203. By also targeting 14-3-3θ, a negative regulator of NF‐κB signaling, miR-203 displayed an overall pro-inflammatory role both in vitro and in vivo. Promoted nuclear translocation of NF‐κB and increased expression of proinflammatory cytokines were observed in cultured BV2 cells transfected with miR-203 mimics. Microglia activation and upregulation of NF‐κB, IL-1β and IL-6 were observed in mouse hippocampus with overexpression of miR-203. In addition, promoted neuronal cell death in the hippocampus and impaired neuronal activities resulted in cognitive dysfunction of mice with ectopic miR-203 expression in the hippocampus. Conclusion A pro-inflammatory and neurodisruptive role of miR-203 was addressed based on our data in this study. Given the identification of Akirin2 as a direct target of miR-203 and the competition with 14-3-3θ for miR-203 targeting, together with the findings of other signaling molecules in NF‐κB pathway as targets of miR-203, we proposed that miR-203 was a master modulator, fine-tunning neuroinflammation by juggling different components of NF‐κB signaling.https://doi.org/10.1186/s12974-022-02451-9NeuroinflammationmiR-203Akirin214-3-3θNF‐κB |
| spellingShingle | Shufang Li Linpeng Li Jieli Li Xiaosheng Liang Chao Song Yi Zou miR-203, fine-tunning neuroinflammation by juggling different components of NF‐κB signaling Journal of Neuroinflammation Neuroinflammation miR-203 Akirin2 14-3-3θ NF‐κB |
| title | miR-203, fine-tunning neuroinflammation by juggling different components of NF‐κB signaling |
| title_full | miR-203, fine-tunning neuroinflammation by juggling different components of NF‐κB signaling |
| title_fullStr | miR-203, fine-tunning neuroinflammation by juggling different components of NF‐κB signaling |
| title_full_unstemmed | miR-203, fine-tunning neuroinflammation by juggling different components of NF‐κB signaling |
| title_short | miR-203, fine-tunning neuroinflammation by juggling different components of NF‐κB signaling |
| title_sort | mir 203 fine tunning neuroinflammation by juggling different components of nf κb signaling |
| topic | Neuroinflammation miR-203 Akirin2 14-3-3θ NF‐κB |
| url | https://doi.org/10.1186/s12974-022-02451-9 |
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