Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease, characterized by Amyloid-β accumulation-induced neuronal injury. Emerging evidence shows that circular RNA (circRNA) is involved in AD development. The aim of this study was to illustrate the role of circ-HUWE1 in Amyloid-β accumulation-induced neuronal injury. Quantitative real-time PCR (qPCR) or western blot was conducted for the expression analysis of circ-HUWE1, miR-433-3p, and fibroblast growth factor 7 (FGF7). In functional assays, cell viability was determined by CCK-8 assay, and cell apoptosis was examined by flow cytometry assay, the protein levels of apoptosis-related markers, and caspase1 or caspase3 activity. The release of pro-inflammatory factors was monitored by ELISA. The predicted binding relationship between miR-433-3p and circ-HUWE1 or FGF7 was validated by dual-luciferase reporter assay. We discovered that circ-HUWE1 absence alleviated Amyloid-β-induced cell viability degradation, cell apoptosis, and inflammatory responses in SK-N-SH cells. MiR-433-3p was a target of circ-HUWE1, and miR-433-3p inhibition reversed the effects of circ-HUWE1 knockdown. In addition, FGF7 was a downstream target of miR-433-3p whose function could be abolished by FGF7 reintroduction. Circ-HUWE1 positively regulated FGF7 expression via competitively targeting miR-433-3p. Moreover, circ-HUWE1 knockdown activated the WNT signaling pathway in Amyloid-β-treated SK-N-SH cells by targeting the miR-433-3p/FGF7 axis. In conclusion, circ-HUWE1 knockdown alleviates Amyloid-β-induced neuronal injury in SK-N-SH cells via miR-433-3p release-mediated FGF7 depletion.
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Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
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This work was supported by the Basic Research and Exploration of Yuzhong District, Chongqing (No. 20200143).
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Yalan Chen and Pei Wang designed and performed the research; Liu Yang and Chenggang Li analyzed the data; Tao Meng wrote the manuscript. All authors read and approved the final manuscript.
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Written informed consents were obtained from all participants, and this study was permitted by the Ethics Committee of Chongqing University Central Hospital. NO. C20200108. The research has been carried out in accordance with the World Medical Association Declaration of Helsinki, and that all subjects provided written informed consent.
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Meng, T., Chen, Y., Wang, P. et al. Circ-HUWE1 Knockdown Alleviates Amyloid-β-Induced Neuronal Injury in SK-N-SH Cells via miR-433-3p Release-Mediated FGF7 Downregulation. Neurotox Res 40, 913–924 (2022). https://doi.org/10.1007/s12640-022-00523-5
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DOI: https://doi.org/10.1007/s12640-022-00523-5