Department of Neurology, Yidu Central Hospital of Weifang, Weifang, China.
Department of Cardiology First Ward, Yidu Central Hospital of Weifang, Weifang, China.
Neuroimmunomodulation. 2022;29(3):211-219. doi: 10.1159/000519780. Epub 2021 Nov 8.
This study aimed to explore the diagnostic value and effect of miR-381-3p on Alzheimer's disease (AD).
RT-qPCR was used for the measurement of miR-381-3p levels. Pearson correlation coefficient was used for the correlation analysis. Receiver operating characteristic (ROC) curve was constructed to assess the distinct ability of miR-381-3p for AD. SH-SY5Y cells were treated with Aβ25-35 to establish an AD cell model. The role of miR-381-3p on cell proliferation and apoptosis was detected. ELISA was applied to detect the protein levels of inflammatory cytokine expression. The target relationship of miR-381-3p with PTGS2 was verified by luciferase reporter gene assay.
Low expression of miR-381-3p was detected in the serum of AD patients and cell models. There was a negative association of serum miR-381-3p with the serum inflammatory cytokines. The ROC curve demonstrated the distinct ability of serum miR-381-3p for AD, with the AUC value of 0.898, with a sensitivity of 87.5%, and a specificity of 77.7%. Overexpression of miR-381-3p reversed the influence of Aβ25-35 on cell proliferation and apoptosis, but miR-381-3p downregulation exacerbated the influence. miR-381-3p overexpression inhibited the release of IL-6, IL-1β, and TNF-α induced by Aβ25-35 treatment, whereas miR-381-3p downregulation further promoted the release of inflammatory cytokines. PTGS2 was the target gene of miR-381-3p and was upregulated in AD cell models.
miR-381-3p is less expressed in the serum of AD patients and has potential diagnostic values for AD. Overexpression of miR-381-3p may attenuate Aβ25-35-induced neurotoxicity and inflammatory responses via targeting PTGS2 in SH-SY5Y cells.
本研究旨在探讨 miR-381-3p 对阿尔茨海默病（AD）的诊断价值和作用。
采用 RT-qPCR 检测 miR-381-3p 水平。采用 Pearson 相关系数进行相关性分析。构建受试者工作特征（ROC）曲线评估 miR-381-3p 对 AD 的诊断能力。用 Aβ25-35 处理 SH-SY5Y 细胞建立 AD 细胞模型。检测 miR-381-3p 对细胞增殖和凋亡的作用。采用 ELISA 检测炎症细胞因子表达的蛋白水平。采用荧光素酶报告基因检测 miR-381-3p 与 PTGS2 的靶向关系。
AD 患者血清和细胞模型中 miR-381-3p 表达水平较低。血清 miR-381-3p 与血清炎症细胞因子呈负相关。ROC 曲线表明血清 miR-381-3p 对 AD 有较好的诊断能力，AUC 值为 0.898，灵敏度为 87.5%，特异性为 77.7%。过表达 miR-381-3p 逆转了 Aβ25-35 对细胞增殖和凋亡的影响，但 miR-381-3p 下调则加剧了这种影响。过表达 miR-381-3p 抑制了 Aβ25-35 诱导的 IL-6、IL-1β 和 TNF-α 的释放，而下调 miR-381-3p 则进一步促进了炎症细胞因子的释放。PTGS2 是 miR-381-3p 的靶基因，在 AD 细胞模型中上调。
AD 患者血清中 miR-381-3p 表达水平降低，对 AD 具有潜在的诊断价值。过表达 miR-381-3p 可能通过靶向 PTGS2 减轻 Aβ25-35 诱导的 SH-SY5Y 细胞神经毒性和炎症反应。
