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. 2025 Jun 7.
doi: 10.1007/s12035-025-05131-w. Online ahead of print.

Exploring the Role of Microglia Activation in Ischemia Stroke Based on the circDnajc1/miR-27a-5p/C1qc Signaling Axis

Shuangping Li #  1   2 , Qingping Ye #  1   2 , Yumeng Li #  1   2 , Jingjing Li  1   2 , Chao Yu  1   2 , Sujun Xue  1   2 , Lijuan Zhang  1   2 , Daiyin Peng  2   3   4   5 , Shizhong Hong  3   4   5   6 , Xianchun Duan  7   8   9   10   11
Affiliations

Exploring the Role of Microglia Activation in Ischemia Stroke Based on the circDnajc1/miR-27a-5p/C1qc Signaling Axis

Shuangping Li et al. Mol Neurobiol. .

Abstract

To date, our understanding of the relationship between middle cerebral artery occlusion/reperfusion (MCAO/R)-induced ischemia stroke and circular RNAs (circRNAs) remains limited. The objective of this research was to explore the roles and underlying mechanisms of the circDnajc1/miR-27a-5p/C1qc signaling pathway in the development of ischemia stroke. For in vitro experiments, an oxygen-glucose deprivation/reperfusion (OGD/R) cell model was established following neuron-microglia co-culture. circDnajc1 siRNA and pcDNA3.1-circDnajc1 overexpression vectors were constructed and transfected into primary microglia. For in vivo experiments, an MCAO/R rat model was established. The molecular mechanisms were investigated using flow cytometry, RT-qPCR, immunofluorescence, RNA immunoprecipitation, and luciferase reporter gene assays. In vitro experiments showed that circDnajc1-induced cellular activation following microglia OGD/R injury, promoted the release of inflammatory factors, downregulated miR-27a-5p, upregulated C1qc, C3, and C5ar, and promotes neuronal apoptosis after microglia OGD/R injury. Interference with circDnajc1 reversed these effects. In vivo experiments, circDnajc1 knockdown exerted a protective effect on neurons in MCAO/R rats and inhibited microglial activation and the release of inflammatory factors. Consistent with the in vitro experiments, circDnajc1 regulated on the expression of downstream target genes of miR-27a-5p, C1qc, C3, and C5ar. CircDnajc1 plays a critical role in ischemia stroke and may influence nervous system homeostasis by regulating the circDnajc1/miR-27a-5p/C1qc signaling axis, which promotes microglia activation and regulates inflammatory factor release and neuronal apoptosis.

Keywords: CircDnajc1; Ischemia; MiR-27a-5p; Microglia; Stroke.

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Conflict of interest statement

Declarations. Ethics Approval and Consent to Participate: The animal experiments have been approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (license number: LLSC20160036). Consent for Publication: Not applicable. Competing interests: The authors declare no competing interests.

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References

    1. Zhang Y, Shen L, Xie J, Li L, Xi W, Li B, Bai Y, Yao H et al (2023) Pushen capsule treatment promotes functional recovery after ischemic stroke. Phytomed Int J Phytother Phytopharmacol 111:154664. https://doi.org/10.1016/j.phymed.2023.154664
    1. Tian D, Pan Y, Zhao Y, Wang H, Tian Y, Yang L, Shi W, Zhang C et al (2023) TCRαβ(+)NK1.1(-)CD4(-)CD8(-) double-negative T cells inhibit central and peripheral inflammation and ameliorate ischemic stroke in mice. Theranostics 13(3):896–909. https://doi.org/10.7150/thno.80307
    1. Zhao S, Zhang P, Yan Y, Xu W, Li J, Wang L, Wang N, Huang Y (2023) Network pharmacology-based prediction and validation of the active ingredients and potential mechanisms of the Huangxiong formula for treating ischemic stroke. J Ethnopharmacol 312:116507. https://doi.org/10.1016/j.jep.2023.116507 - DOI - PubMed
    1. Alhazmi H, Bani-Sadr A, Bochaton T, Paccalet A, Da Silva CC, Buisson M, Amaz C, Ameli R et al (2021) Large vessel cardioembolic stroke and embolic stroke of undetermined source share a common profile of matrix metalloproteinase-9 level and susceptibility vessel sign length. Eur J Neurol 28(6):1977–1983. https://doi.org/10.1111/ene.14806
    1. Cai W, Hu M, Li C, Wu R, Lu D, Xie C, Zhang W, Li T et al (2023) FOXP3+ macrophage represses acute ischemic stroke-induced neural inflammation. Autophagy 19(4):1144–1163. https://doi.org/10.1080/15548627.2022.2116833

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