长链非编码 RNA MEG8 通过 miR-485-3p/FBXO45 轴减轻帕金森病神经炎症。
LncRNA MEG8 ameliorates Parkinson's disease neuro-inflammation through miR-485-3p/FBXO45 axis.
机构信息
Department of Neurology, Taizhou Central Hospital (Taizhou University Hospital), No.999, Donghai Avenue, Jiaojiang District, Taizhou, 318000, Zhejiang, China.
出版信息
Acta Neurol Belg. 2024 Apr;124(2):549-557. doi: 10.1007/s13760-023-02388-7. Epub 2023 Oct 9.
OBJECTIVE
Studies suggest that LncRNA maternally expressed 8, small nucleolar RNA host gene (MEG8) contributes to inflammatory regulation, while the function and potential mechanisms of MEG8 in Parkinson's disease (PD) are unknown. This study aimed to assess the clinical value and biological function of MEG8 in PD.
METHODS
One hundred and two PD patients, eighty-six AD patients, and eighty healthy controls were enrolled in this study. Lipopolysaccharide (LPS)-induced microglia BV2 constructs an in vitro cell model. RT-qPCR was conducted to quantify the levels of MEG8, miR-485-3p, and FBXO45 in serum and cells. ROC curve was employed to examine the diagnostic value of MEG8 in PD. Serum and cellular pro-inflammatory factor secretion were quantified by ELISA. Dual-luciferase reporter and RIP assay to validate the targeting relationship between miR-485-3p and FBXO45.
RESULTS
MEG8 and FBXO45 were significantly decreased in the serum of PD patients and LPS-induced bv2, while miR-485-3p was increased (P < 0.05). ROC curve confirmed that serum MEG8 has high sensitivity and specificity to identify PD patients from healthy controls and AD patients, respectively. Elevated MEG8 alleviated LPS-induced inflammatory factor overproduction compared with LPS-induced BV2 (P < 0.05), but this alleviating effect was eliminated by miR-485-3p (P < 0.05). The LPS-induced inflammatory response was suppressed by the low expression of miR-485-3p but significantly reversed by silencing of FBXO45. MEG8 was a sponge for miR-485-3p and inhibited its levels and promoted FBXO45 expression (P < 0.05).
CONCLUSION
Elevated MEG8 is a potential diagnostic biomarker for PD and may mitigate inflammatory damage in PD via the miR-485-3p/FBXO45 axis.
目的
研究表明长链非编码 RNA 母系表达基因 8（MEG8）有助于炎症调节，而 MEG8 在帕金森病（PD）中的功能和潜在机制尚不清楚。本研究旨在评估 MEG8 在 PD 中的临床价值和生物学功能。
方法
本研究纳入了 102 例 PD 患者、86 例 AD 患者和 80 名健康对照者。采用脂多糖（LPS）诱导的小胶质细胞 BV2 构建体外细胞模型。通过 RT-qPCR 定量血清和细胞中 MEG8、miR-485-3p 和 FBXO45 的水平。ROC 曲线评估 MEG8 在 PD 中的诊断价值。通过 ELISA 定量测定血清和细胞中促炎因子的分泌。双荧光素酶报告和 RIP 测定验证 miR-485-3p 与 FBXO45 的靶向关系。
结果
PD 患者血清和 LPS 诱导的 bv2 中 MEG8 和 FBXO45 显著降低，而 miR-485-3p 升高（P<0.05）。ROC 曲线证实血清 MEG8 对 PD 患者与健康对照者和 AD 患者的区分具有较高的灵敏度和特异性。与 LPS 诱导的 BV2 相比，升高的 MEG8 减轻了 LPS 诱导的炎症因子过度产生（P<0.05），但这种缓解作用被 miR-485-3p 消除（P<0.05）。miR-485-3p 的低表达抑制了 LPS 诱导的炎症反应，但沉默 FBXO45 则显著逆转了这种抑制作用。MEG8 是 miR-485-3p 的海绵，可降低其水平并促进 FBXO45 表达（P<0.05）。
结论
升高的 MEG8 可能是 PD 的潜在诊断生物标志物，可通过 miR-485-3p/FBXO45 轴减轻 PD 中的炎症损伤。
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