Background

Numerous microRNAs (miRNAs) have been investigated in the progression of Alzheimer's disease (AD). The purpose of this study was to analyze the expression of miR-433 and its diagnostic value in patients with AD, and to explore the neuroprotective effect of miR-433 in amyloid β (Aβ)-treated SH-SY5Y and SK-N-SH cells.

Methods

AD patients and AD cell model that established by Aβ treatment were used in this study. Quantitative real-time PCR was used to measure the expression of miR-433. The diagnostic value of miR-433 was evaluated using the receiver operating characteristic analysis. MTT assay was used to examine the viability of Aβ-treated SH-SY5Y and SK-N-SH cells. Bioinformatics and luciferase activity analyses were used to confirm the target gene that might be involved in the mechanisms of miR-433 in AD.

Results

Expression levels of miR-433 were decreased in AD patients and cells compared with the corresponding controls. The decreased miR-433 expression levels in serum and cerebrospinal fluid (CS) were positively correlated with MMSE scores and had relatively high diagnostic accuracy in AD patients. The gain-of-function experiments found that the overexpression of miR-433 could rescue the Aβ-induced inhibition in neuronal viability in SH-SY5Y and SK-N-SH cells. The luciferase activity results showed that JAK2 was a target gene of miR-433 in neuronal cells.

Conclusion

All the data of this study showed that miR-433 serves as a candidate diagnostic biomarker for AD patients, and may have the potential as a novel therapeutic target by ameliorating Aβ-induced neurotoxicity.

中文翻译：

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miR-433在阿尔茨海默病诊断中的临床意义及其通过调节JAK2对Aβ诱导的神经毒性的影响。

背景

已经在阿尔茨海默病 (AD) 的进展中研究了许多 microRNA (miRNA)。本研究的目的是分析 miR-433 在 AD 患者中的表达及其诊断价值，并探讨 miR-433 在淀粉样蛋白 β (Aβ) 治疗的 SH-SY5Y 和 SK-N-SH 中的神经保护作用。细胞。

方法

本研究使用AD患者和Aβ处理建立的AD细胞模型。定量实时PCR用于测量miR-433的表达。使用受试者工作特征分析评估 miR-433 的诊断价值。MTT测定用于检查Aβ处理的SH-SY5Y和SK-N-SH细胞的活力。生物信息学和荧光素酶活性分析用于确认可能参与AD中miR-433机制的靶基因。

结果

与相应的对照相比，AD 患者和细胞中 miR-433 的表达水平降低。血清和脑脊液（CS）中 miR-433 表达水平降低与 MMSE 评分呈正相关，在 AD 患者中具有较高的诊断准确性。功能获得实验发现，过表达 miR-433 可以挽救 Aβ 诱导的 SH-SY5Y 和 SK-N-SH 细胞中神经元活力的抑制。荧光素酶活性结果显示JAK2是miR-433在神经元细胞中的靶基因。

结论

本研究的所有数据表明，miR-433 可作为 AD 患者的候选诊断生物标志物，并可能通过改善 Aβ 诱导的神经毒性作为新的治疗靶点。