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阿尔茨海默病中 miR-148a-3p 的异常表达及其对淀粉样β诱导的神经毒性的保护作用。

Aberrant expression of miR-148a-3p in Alzheimer's disease and its protective role against amyloid-β induced neurotoxicity.

机构信息

The First Department of Neurology, Rizhao People's Hospital, Rizhao, 276800, Shandong, China.

Department of Neurology, Zhucheng People's Hospital, Zhucheng, 262200, Shandong, China.

出版信息

Neurosci Lett. 2021 Jun 21;756:135953. doi: 10.1016/j.neulet.2021.135953. Epub 2021 May 9.

DOI:10.1016/j.neulet.2021.135953
PMID:33979697
Abstract

OBJECTIVE

The current study investigated the expression change and clinical value of miR-148a-3p in AD patients, and further examined the role of miR-148a-3p in Aβ-induced neurotoxicity in SH-SY5Y cells.

MATERIAL AND METHODS

qRT-PCR was used for the measurement of miR-148a-3p expression levels. ROC curve was established to calculate the diagnostic value of serum miR-148a-3p for AD. CCK-8 and flow cytometry assay was applied for the detection of cell viability and apoptosis. Additionally, the luciferase reporter assay was performed to confirm the target relationship between ROCK1 and miR-148a-3p.

RESULTS

Serum miR-148a-3p was downregulated in AD patients compared with that in healthy controls, and was positively associated with the MMSE score in AD patients. Serum miR-148a-3p had the potential to distinguish AD patients from healthy controls, and the diagnostic sensitivity and specificity were respectively 85.5 % and 87.0 % at a cutoff value of 0.827. MiR-148a-3p attenuated Aβ25-35 induced neurotoxicity in SH-SY5Y cells, and ROCK1 was the target gene.

CONCLUSION

Serum miR-148a-3p is correlated with MMSE score in AD patients, and it might be helpful for the AD diagnosis. Overexpression of miR-148a-3p attenuated Aβ induced neurotoxicity in AD by targeting ROCK1.

摘要

目的

本研究旨在探讨 miR-148a-3p 在 AD 患者中的表达变化及其临床价值,并进一步研究 miR-148a-3p 在 Aβ 诱导的 SH-SY5Y 细胞神经毒性中的作用。

材料与方法

采用 qRT-PCR 检测 miR-148a-3p 的表达水平。绘制 ROC 曲线,计算血清 miR-148a-3p 对 AD 的诊断价值。CCK-8 和流式细胞术检测细胞活力和凋亡。此外,还进行了荧光素酶报告基因实验来验证 ROCK1 与 miR-148a-3p 之间的靶关系。

结果

与健康对照组相比,AD 患者血清 miR-148a-3p 表达下调,且与 AD 患者 MMSE 评分呈正相关。血清 miR-148a-3p 具有区分 AD 患者与健康对照组的潜力,截断值为 0.827 时,诊断的敏感性和特异性分别为 85.5%和 87.0%。miR-148a-3p 可减轻 Aβ25-35 诱导的 SH-SY5Y 细胞神经毒性,ROCK1 是其靶基因。

结论

血清 miR-148a-3p 与 AD 患者的 MMSE 评分相关,可能有助于 AD 的诊断。过表达 miR-148a-3p 通过靶向 ROCK1 减轻 Aβ 诱导的 AD 神经毒性。

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