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Circ_0057583 facilitates brain microvascular endothelial cell injury through modulating miR-204-5p/NR4A1 axis

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Abstract

Lipopolysaccharide (LPS) can induce vascular endothelial injury. Circular RNAs (circRNAs) have been verified to regulate different cellular processes in various diseases. This study intended to explore the potential role and mechanism of circ_0057583 in brain microvascular endothelial cell injury. Human brain microvascular endothelial cells (hBMECs) were exposed to different doses of LPS to induce cell damage. The levels of circ_0057583, microRNA-204-5p (miR-204-5p) and nuclear receptor 4A1 (NR4A1) were detected by quantitative real-time PCR or Western blot assays. Cell viability, apoptosis, inflammation and angiogenesis were assessed by Counting Kit-8 (CCK-8), flow cytometry, enzyme linked immunosorbent assay (ELISA) and tube formation assays. The targeting relationship between miR-204-5p and circ_0057583 or NR4A1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. LPS treatment elevated the expression of circ_0057583 and NR4A1, but decreased the expression of miR-204-5p in LPS-induced hBMECs. Downregulation of circ_0057583 abated LPS-induced hBMEC injury by inducing cell proliferation and angiogenesis, as well as inhibiting cell apoptosis, autophagy and inflammation. Circ_0057583 aggravated LPS-evoked hBMEC injury by regulating miR-204-5p. Also, miR-204-5p suppressed LPS-evoked hBMEC damage via targeting NR4A1. Moreover, circ_0057583 sponged miR-204-5p to up-regulate NR4A1 level. Depletion of circ_0057583 alleviated LPS-triggered brain microvascular endothelial endothelial cell injury through modulating miR-204-5p/NR4A1 axis.

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Data availability statement

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by Medical Science and Technology Research Project of Henan Province (No. LHGJ20190809). Scientific and Technological Talents Overseas Training Project (No.2018151).

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Author notes

  1. Xiaoyu Wang and Lili Liu Contributed equally.

Authors and Affiliations

  1. Department of Medicine Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, 450003, China

    Xiaoyu Wang, Lei Zhang, Jing Guo, Lixia Yu & Tao Li

  2. Department of Neorology, Ninth People’s Hospital of Zhengzhou, Zhengzhou, 450012, China

    Lili Liu

  3. Department of Medicine Laboratory, Henan Provincial People’s Hospital, Zhengzhou, 450003, China

    Tao Li

  4. Central China Fuwai Hospital of Zhengzhou University, No.1 Fuwai Road, Zhengdong New District, Zhengzhou, 450003, China

    Tao Li

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  1. Xiaoyu Wang
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  2. Lili Liu
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  3. Lei Zhang
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  4. Jing Guo
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  5. Lixia Yu
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Contributions

Tao Li designed and supervised the study. Xiaoyu Wang and Lili Liu conducted the experiments and drafted the manuscript. Lei Zhang collected and analyzed the data. Jing Guo contributed the methodology and analyzed the data. Lixia Yu edited the manuscript.

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Correspondence to Tao Li.

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Wang, X., Liu, L., Zhang, L. et al. Circ_0057583 facilitates brain microvascular endothelial cell injury through modulating miR-204-5p/NR4A1 axis. Metab Brain Dis 37, 501–511 (2022). https://doi.org/10.1007/s11011-021-00866-6

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  • DOI: https://doi.org/10.1007/s11011-021-00866-6

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