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MiRNA-494-3p Regulates Bupivacaine-Induced Neurotoxicity by the CDK6-PI3K/AKT Signaling

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Abstract

Bupivacaine (BUP) is a long-acting amide local anesthetic that may induce strong neurotoxicity and neurological complications. In this study, we elucidate the influence of microRNA-494-3p (miR-494-3p) in BUP-induced neurotoxicity in primary mouse hippocampal neuronal cells. In this study, primary hippocampal neurons were isolated from neonatal C57BL/6 mice. The isolated neurons were treated with various doses of BUP. MTT assay was conducted to analyze neuronal viability. Gene expression measurement was done by RT-qPCR. The impact of miR-494-3p in BUP-mediated neural injury was examined using TUNEL, flow cytometry, western blotting, and ROS activity detection. The regulatory relationship between miR-494-3p and cyclin-dependent kinases 4 and 6 (CDK6) was identified using a luciferase reporter assay. BUP treatment led to neurotoxicity and miR-494-3p upregulation in primary cultured hippocampal neurons. Functionally, miR-494-3p depletion alleviated neuronal apoptosis and oxidative damage induced by BUP. We verified that miR-494-3p targeted and negatively modulated CDK6. MiR-494-3p depletion also activated PI3K/AKT signaling by elevating CDK6 expression in BUP-treated neurons. Furthermore, CDK6 knockdown or PI3K/AKT inactivation attenuated the neuroprotective role of miR-494-3p depletion. Silencing miR-494-3p exerts neuroprotective function in hippocampal neuronal cells against BUP-induced injury by the CDK6-PI3K/AKT pathway.

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Author notes

  1. Licheng Zhang and Lifeng Zhang contributed equally to the work.

Authors and Affiliations

  1. Deparment of Anesthesia Resuscitation Room, Zhongshan Hospital Xiamen University, Xiamen, Fujian, 361004, China

    Licheng Zhang

  2. Deparment of Surgical Anesthesiology, Zhongshan Hospital Xiamen University, Xiamen, Fujian, 361004, China

    Lifeng Zhang

  3. Department of Tumor Radiotherapy, Zhongshan Hospital Xiamen University, Siming District, 1854 Xinjing Garden, Luling Road, Xiamen, 361004, Fujian, China

    Fengying Guo

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  1. Licheng Zhang
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  2. Lifeng Zhang
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  3. Fengying Guo
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Correspondence to Fengying Guo.

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Zhang, L., Zhang, L. & Guo, F. MiRNA-494-3p Regulates Bupivacaine-Induced Neurotoxicity by the CDK6-PI3K/AKT Signaling. Neurotox Res 39, 2007–2017 (2021). https://doi.org/10.1007/s12640-021-00427-w

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  • DOI: https://doi.org/10.1007/s12640-021-00427-w

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