miR-485-3p在帕金森病患者中的诊断价值及其与神经炎症的关系

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2022-06-01 Epub Date: 2021-07-19 DOI:10.1007/s12017-021-08676-w
Xia Lin, Rui Wang, Ran Li, Taotao Tao, Danhong Zhang, Yuxiang Qi
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引用次数: 14

摘要

帕金森病(PD)是最常见的进行性神经退行性疾病之一。一些microRNAs (miRNAs)在许多神经系统疾病的发展中起着至关重要的作用。本研究旨在评价miR-485-3p在PD发生发展中的临床意义及生物学功能。采用实时荧光定量PCR (qRT-PCR)分析PD患者血清中miR-485-3p的表达。lps处理的小胶质细胞BV2细胞被用来模拟PD发病机制中的神经炎症。采用酶联免疫吸附法(ELISA)检测各组炎症因子IL-1β、IL-6、TNF-α水平。通过绘制受试者工作特征(ROC)曲线评价miR-485-3p的诊断价值。荧光素酶报告基因检测证实了miR-485-3p和FBXO45之间的相互作用。结果显示,与阿尔茨海默病(AD)和健康人相比,PD患者血清中miR-485-3p均显著上调,具有诊断PD筛查的准确性。LPS诱导的活化的小胶质细胞BV2细胞miR-485-3p也升高,miR-485-3p的敲低抑制了促炎细胞因子的释放。FBXO蛋白45 (FBXO45)作为miR-485-3p的潜在靶点,推测其介导miR-485-3p的功能。我们的研究结果表明,miR-485-3p在PD中的上调表达可能是PD的一种新的诊断生物标志物。降低miR-485-3p的表达水平可以抑制BV2细胞的炎症反应,这表明miR-485-3p作为神经炎症的调节剂,可能具有作为PD治疗靶点的潜力。
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Diagnostic Performance of miR-485-3p in Patients with Parkinson's Disease and its Relationship with Neuroinflammation.

Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. Some microRNAs (miRNAs) play critical roles in the development of many neurological diseases. This study aims to evaluate the clinical significance and biological function of miR-485-3p in the development and progression of PD. The expression of miR-485-3p in serum of PD patients was analyzed by quantitative real-time PCR (qRT-PCR). LPS-treated microglia BV2 cells were used to mimic neuroinflammation in the pathogenesis of PD. The levels of inflammatory cytokines, including IL-1β, IL-6 and TNF-α, were detected by enzyme-linked immunosorbent assay (ELISA). The diagnosis value of miR-485-3p was evaluated by plotting receiver operating characteristic (ROC) curves. A luciferase reporter assay was performed to demonstrate the interaction between miR-485-3p and FBXO45. The results showed that miR-485-3p was significantly up-regulated in serum of PD patients compared with that in both Alzheimer's disease (AD) and healthy cases, and had diagnostic accuracy for PD screening. The activated microglia BV2 cells induced by LPS also had elevated miR-485-3p, and the knockdown of miR-485-3p inhibited the release of pro-inflammatory cytokines. FBXO protein 45 (FBXO45) served as a potential target of miR-485-3p, which was speculated to mediate the function of miR-485-3p. Our results suggest that the up-regulated expression of miR-485-3p in PD may be a novel diagnostic biomarker for PD. Reducing the expression level of miR-485-3p can inhibit the inflammatory responses of BV2 cells, which indicated that miR-485-3p, as a regulator of neuroinflammation, may have the potential as a therapeutic target in PD.

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