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微小RNA-133b是阿尔茨海默病的一种潜在诊断生物标志物,具有神经保护作用。

miR-133b is a potential diagnostic biomarker for Alzheimer's disease and has a neuroprotective role.

作者信息

Yang Qin, Zhao Qiuling, Yin Yanliang

机构信息

Department of Neurology, Dongying People's Hospital, Dongcheng, Shandong 257091, P.R. China.

Digestive Endoscopy Center, Dongying People's Hospital, Dongcheng, Shandong 257091, P.R. China.

出版信息

Exp Ther Med. 2019 Oct;18(4):2711-2718. doi: 10.3892/etm.2019.7855. Epub 2019 Aug 5.

Abstract

MicroRNAs (miRNAs/miRs) are involved in post-transcriptional gene regulation and aberrant expression of miRNAs has been widely detected in various human diseases. The aim of the present study was to examine the serum levels of miR-133b in patients with Alzheimer's disease (AD), and to explore its diagnostic value and neuroprotective role in AD. Reverse transcription-quantitative PCR was applied to analyze the serum levels of miR-133b in 105 AD patients and 98 healthy controls. A cell model of AD was established by treating SH-SY5Y cells with amyloid β (Aβ)25-35, and the resulting effect on miR-133b expression was determined. Cell viability and apoptosis were also measured. A dual-luciferase assay was used to validate a target gene of miR-133b. Receiver operating characteristic (ROC) curve analysis was also applied to assess the specificity and sensitivity of miR-133b to diagnose AD. The results indicated that the serum levels of miR-133b were significantly downregulated in AD patients and SH-SY5Y cells treated with Aβ25-35 (all P<0.001). A positive correlation between the serum levels of miR-133b and the Mini-Mental State Examination score of AD patients was determined (r=0.8814, P<0.001). The area under the ROC curve for miR-133b regarding the diagnosis of AD was 0.907, with a sensitivity of 90.8% and specificity of 74.3% at the cutoff value of 1.70. Overexpression of miR-133b significantly attenuated the Aβ25-35-induced inhibition of cell viability (P<0.01) and induction of cell apoptosis (P<0.01). The luciferase reporter assay demonstrated that epidermal growth factor receptor (EGFR) is a target gene of miR-133b. In conclusion, miR-133b may serve as a novel diagnostic biomarker for AD and it may have a neuroprotective role in AD and targets EGFR.

摘要

微小RNA(miRNA/miR)参与转录后基因调控,且在多种人类疾病中广泛检测到miRNA的异常表达。本研究的目的是检测阿尔茨海默病(AD)患者血清中miR-133b的水平,并探讨其在AD中的诊断价值和神经保护作用。应用逆转录定量PCR分析105例AD患者和98例健康对照者血清中miR-133b的水平。用淀粉样β蛋白(Aβ)25-35处理SH-SY5Y细胞建立AD细胞模型,并测定其对miR-133b表达的影响。同时检测细胞活力和凋亡情况。采用双荧光素酶报告基因检测法验证miR-133b的靶基因。应用受试者工作特征(ROC)曲线分析评估miR-133b诊断AD的特异性和敏感性。结果表明,AD患者及用Aβ25-35处理的SH-SY5Y细胞中miR-133b的血清水平均显著下调(均P<0.001)。确定AD患者血清miR-133b水平与简易精神状态检查表评分呈正相关(r=0.8814,P<0.001)。miR-133b诊断AD的ROC曲线下面积为0.907,在临界值为1.70时,敏感性为90.8%,特异性为74.3%。miR-133b过表达显著减轻Aβ25-35诱导的细胞活力抑制(P<0.01)和细胞凋亡诱导(P<0.01)。荧光素酶报告基因检测表明表皮生长因子受体(EGFR)是miR-133b的靶基因。总之,miR-133b可能作为AD的一种新型诊断生物标志物,且在AD中可能具有神经保护作用并靶向EGFR。

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