It is vital to understand the mechanism of epilepsy onset and development. Dysregulated lncRNAs are closely associated with epilepsy. Our work probed the role of lncRNA PVT1/miR-488-3p/FOXD3/SCN2A axis in epilepsy. The mRNA and protein expressions were assessed using qRT-PCR and western blot. MTT assay and TUNEL staining were conducted to assess cell viability and apoptosis, respectively. TNFα, IL-1β and IL-6 levels were analyzed using ELISA. LDH level was tested by Assay Kit. The binding relationship between PVT1, miR-488-3p and FOXD3 were verified using dual luciferase reporter gene assay. The epilepsy model of rats was established by lithium-pilocarpine injection. Nissl staining was performed to evaluate neuronal damage. PVT1 was markedly upregulated in epilepsy model cells. Knockdown of PVT1 increased the viability, while repressed the apoptosis and inflammatory cytokines secretion as well as LDH level in epilepsy cell model. MiR-488-3p alleviated neuronal injury and neuroinflammation in model cells. MiR-488-3p functioned as the direct target of PVT1, and its inhibition neutralized the effects of PVT1 silencing on neuronal cell injury and neuroinflammation in model cells. Furthermore, miR-488-3p inhibited neuronal cell injury and neuroinflammation in model cells by regulating FOXD3/SCN2A pathway. Finally, animal experiments proved that PVT1 promoted epilepsy-induced neuronal cell injury and neuroinflammation by regulating miR-488-3p-mediated FOXD3/SCN2A pathway. PVT1 promoted neuronal cell injury and inflammatory response in epilepsy via inhibiting miR-488-3p and further regulating FOXD3/SCN2A pathway.

了解癫痫发作和发展的机制至关重要。失调的 lncRNA 与癫痫密切相关。我们的工作探讨了 lncRNA PVT1/miR-488-3p/FOXD3/SCN2A 轴在癫痫中的作用。使用 qRT-PCR 和蛋白质印迹评估 mRNA 和蛋白质表达。进行MTT测定和TUNEL染色以分别评估细胞活力和细胞凋亡。使用 ELISA 分析 TNFα、IL-1β 和 IL-6 水平。LDH 水平由 Assay Kit 检测。使用双荧光素酶报告基因测定法验证 PVT1、miR-488-3p 和 FOXD3 之间的结合关系。采用锂毛果芸香碱注射液建立大鼠癫痫模型。进行尼氏染色以评估神经元损伤。PVT1 在癫痫模型细胞中显着上调。PVT1 的击倒增加了生存能力，同时抑制癫痫细胞模型中的细胞凋亡和炎性细胞因子分泌以及 LDH 水平。MiR-488-3p 减轻了模型细胞中的神经元损伤和神经炎症。MiR-488-3p 作为 PVT1 的直接靶标，其抑制作用中和了 PVT1 沉默对模型细胞神经元细胞损伤和神经炎症的影响。此外，miR-488-3p 通过调节 FOXD3/SCN2A 通路抑制模型细胞的神经元细胞损伤和神经炎症。最后，动物实验证明PVT1通过调节miR-488-3p介导的FOXD3/SCN2A通路促进癫痫引起的神经元细胞损伤和神经炎症。PVT1 通过抑制 miR-488-3p 并进一步调节 FOXD3/SCN2A 通路促进癫痫神经元细胞损伤和炎症反应。