Du Wenyan, Lei Chengbin, Dong Yong
Zibo Central Hospital, Department of Science and Education, Zibo, Shandong, China.
Zibo Central Hospital, Department of Clinical Laboratory, Zibo, Shandong, China.
Genet Mol Biol. 2021 Jan 11;44(1):e20200064. doi: 10.1590/1678-4685-GMB-2020-0064. eCollection 2021.
Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) plays a critical role in Alzheimer's disease (AD) pathogenesis. This study aimed to investigate the relationship between microRNA-149 (miR-149) and BACE1, and evaluate the clinical significance and biological function of miR-149 in AD progression. Bioinformatics analysis and a luciferase reporter assay were used to confirm the interaction between miR-149 and BACE1. Expression of miR-149 and BACE1 was estimated using quantitative real-time PCR. The clinical significance of miR-149 in AD diagnosis and severity determination was evaluated using ROC analysis. The effect of miR-149 on Aβ accumulation and neuronal viability was analyzed in Aβ-treated SH-SY5Y cells. miR-149 was found directly binding the 3'-UTR of BACE1 and was negatively correlated with BACE1 in AD patients and cell model. Serum miR-149 expression was downregulated in AD patients and served as a potential diagnostic biomarker. The overexpression of miR-149 in Aβ-treated SH-SY5Y cells resulted in inhibited Aβ accumulation and enhanced neuronal viability. This study demonstrated that serum miR-149 is decreased in AD patients and serves as a candidate diagnostic biomarker, and that the overexpression of miR-149 may suppress Aβ accumulation and promote neuronal viability by targeting BACE1 in AD model cells.
β-位点淀粉样前体蛋白裂解酶1（BACE1）在阿尔茨海默病（AD）发病机制中起关键作用。本研究旨在探讨微小RNA-149（miR-149）与BACE1之间的关系，并评估miR-149在AD进展中的临床意义和生物学功能。采用生物信息学分析和荧光素酶报告基因检测来证实miR-149与BACE1之间的相互作用。使用定量实时PCR评估miR-149和BACE1的表达。采用ROC分析评估miR-149在AD诊断和病情严重程度判定中的临床意义。在经Aβ处理的SH-SY5Y细胞中分析miR-149对Aβ积累和神经元活力的影响。发现miR-149直接结合BACE1的3'-UTR，且在AD患者和细胞模型中与BACE1呈负相关。AD患者血清miR-149表达下调，可作为潜在的诊断生物标志物。在经Aβ处理的SH-SY5Y细胞中过表达miR-149可抑制Aβ积累并增强神经元活力。本研究表明，AD患者血清miR-149降低，可作为候选诊断生物标志物，且在AD模型细胞中过表达miR-149可能通过靶向BACE1抑制Aβ积累并促进神经元活力。
