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Diagnostic value of miR-193a-3p in Alzheimer's disease and miR-193a-3p attenuates amyloid-β induced neurotoxicity by targeting PTEN.
Experimental Gerontology ( IF 3.9 ) Pub Date : 2019-12-16 , DOI: 10.1016/j.exger.2019.110814
Fengjun Cao 1 , Zhongjie Liu 1 , Guanjun Sun 1
Affiliation  

OBJECTIVE Many microRNAs (miRNAs) have been reported to be aberrantly expressed in Alzheimer's disease (AD) patients. The present study aimed to explore the diagnostic value and neuroprotective role of miR-193a-3p in AD. METHODS 108 sporadic AD patients and 93 healthy controls were included. An Aβ25-35 insult cellular AD model of PC12 and SH-SY5Y was established. The relative expression levels of miR-193a-3p were calculated using qRT-PCR. Receiver operating characteristic (ROC) curve was applied to evaluate the usefulness of miR-193a-3p for detecting AD. Cell viability and apoptotic rates were calculated. Luciferase reporter assay was performed to confirm the interaction between miR-193a-3p and PTEN. RESULTS miR-193a-3p expression was downregulated in both AD patients and the cellular AD model (all P < 0.001). Remarkable positive association was detected between serum miR-193a-3p level and MMSE score in AD patients (r = 0.5889, P < 0.0001). The diagnostic sensitivity and specificity were 89.8% and 77.4%, respectively, and the area under the curve (AUC) was 0.914. Overexpression of miR-193a-3p weakened Aβ25-35 induced cell viability inhibition, and reduced Aβ25-35 induced cell apoptosis in PC12 cells (all P < 0.01). Downregulation of miR-193a-3p intensified the effect of Aβ25-35 PTEN was proved to be the target gene of miR-193a-3p. CONCLUSION MiR-193a-3p could be a novel biomarker for AD diagnosis, and may protect against neurotoxicity in AD by targeting PTEN.

中文翻译:

miR-193a-3p对阿尔茨海默氏病和miR-193a-3p的诊断价值通过靶向PTEN来减轻淀粉样β诱导的神经毒性。

目的据报道,许多微RNA(miRNA)在阿尔茨海默氏病(AD)患者中异常表达。本研究旨在探讨miR-193a-3p在AD中的诊断价值和神经保护作用。方法包括108例散发性AD患者和93例健康对照者。建立了PC12和SH-SY5Y的Aβ25-35侵袭性细胞AD模型。使用qRT-PCR计算miR-193a-3p的相对表达水平。接收器工作特性(ROC)曲线用于评估miR-193a-3p对检测AD的有用性。计算细胞活力和凋亡率。进行荧光素酶报告基因测定以证实miR-193a-3p和PTEN之间的相互作用。结果AD患者和细胞AD模型中miR-193a-3p表达均下调(所有P <0.001)。在AD患者中,血清miR-193a-3p水平与MMSE评分之间存在显着的正相关性(r = 0.5889,P <0.0001)。诊断灵敏度和特异性分别为89.8%和77.4%,曲线下面积(AUC)为0.914。miR-193a-3p的过表达减弱了PC12细胞中Aβ25-35诱导的细胞活力抑制,并降低了Aβ25-35诱导的细胞凋亡(所有P <0.01)。miR-193a-3p的下调增强了Aβ25-35PTEN的作用,被证明是miR-193a-3p的目标基因。结论MiR-193a-3p可能是AD诊断的新型生物标志物,可以通过靶向PTEN来预防AD的神经毒性。曲线下面积(AUC)为0.914。miR-193a-3p的过表达减弱了PC12细胞中Aβ25-35诱导的细胞活力抑制,并降低了Aβ25-35诱导的细胞凋亡(所有P <0.01)。miR-193a-3p的下调增强了Aβ25-35PTEN的作用,被证明是miR-193a-3p的目标基因。结论MiR-193a-3p可能是AD诊断的新型生物标志物,可以通过靶向PTEN来预防AD的神经毒性。曲线下面积(AUC)为0.914。miR-193a-3p的过表达减弱了PC12细胞中Aβ25-35诱导的细胞活力抑制,并降低了Aβ25-35诱导的细胞凋亡(所有P <0.01)。miR-193a-3p的下调增强了Aβ25-35PTEN的作用,被证明是miR-193a-3p的目标基因。结论MiR-193a-3p可能是AD诊断的新型生物标志物,可以通过靶向PTEN来预防AD的神经毒性。
更新日期:2019-12-17
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