Liu Yan, Xu Yuhao, Yu Ming
Department of Neurology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
Exp Ther Med. 2022 Mar;23(3):241. doi: 10.3892/etm.2022.11166. Epub 2022 Jan 26.
The aim of the present study was to investigate the expression levels of microRNA(miR)-4722-5p and miR-615-3p in Alzheimer's disease (AD) and their diagnostic value. Blood samples were collected from 33 patients with AD and 33 healthy controls, and an β-amyloid (Aβ)25-35-induced PC12 cell model was also established. The relative mRNA expression levels of miR-4722-5p and miR-615-3p were detected using reverse transcription-quantitative PCR. The correlations between the mRNA expression levels of the two miRNAs and the mini-mental state examination (MMSE) scores were analyzed, and the receiver operating characteristic curve was used to assess the diagnostic value of miR-4722-5p and miR-615-3p in AD. Functional enrichment analysis of the miRNA target genes was performed using The Database for Annotation, Visualization and Integrated Discovery database and the R language analysis package. The mRNA expression levels of miR-4722-5p and miR-615-3p were increased in patients with AD and the Aβ25-35-induced PC12 cell model. The mRNA expression levels of miR-4722-5p and miR-615-3p were negatively correlated with MMSE scores, and the combination of the two miRNAs for AD had an improved diagnostic value than that of each miRNA alone. The results of Gene Ontology (GO) enrichment analysis showed that the target genes of miR-4722-5p were found in the cytoplasm and cytosol, and were mainly involved in protein folding and cell division. The molecular functions included protein binding and GTPase activator activity. The results of Kyoto Encyclopedia of Genes and Genomes analysis showed that miR-4722-5p was associated with the regulation of dopaminergic synapses and mTOR signaling pathways. GO enrichment analysis also revealed that the target genes of miR-615-3p were located in the nucleus and cytoplasm, were involved in the regulation of transcription and protein phosphorylation, and were associated with protein binding, metal ion binding and transcription factor activity. The target genes of miR-615-3p played important roles in the regulation of the Ras and FoxO signaling pathways. In conclusion, miR-4722-5p and miR-615-3p may be potential biomarkers in the early diagnosis of AD.
本研究旨在探讨微小RNA（miR）-4722-5p和miR-615-3p在阿尔茨海默病（AD）中的表达水平及其诊断价值。收集了33例AD患者和33名健康对照者的血液样本，并建立了β-淀粉样蛋白（Aβ）25-35诱导的PC12细胞模型。采用逆转录定量PCR检测miR-4722-5p和miR-615-3p的相对mRNA表达水平。分析了这两种微小RNA的mRNA表达水平与简易精神状态检查表（MMSE）评分之间的相关性，并使用受试者工作特征曲线评估miR-4722-5p和miR-615-3p在AD中的诊断价值。使用注释、可视化和综合发现数据库以及R语言分析包对微小RNA靶基因进行功能富集分析。在AD患者和Aβ25-35诱导的PC12细胞模型中，miR-4722-5p和miR-615-3p的mRNA表达水平升高。miR-4722-5p和miR-615-3p的mRNA表达水平与MMSE评分呈负相关，两种微小RNA联合用于AD诊断的价值优于单独使用每种微小RNA。基因本体论（GO）富集分析结果显示，miR-4722-5p的靶基因存在于细胞质和胞质溶胶中，主要参与蛋白质折叠和细胞分裂。分子功能包括蛋白质结合和GTP酶激活剂活性。京都基因与基因组百科全书分析结果显示，miR-4722-5p与多巴胺能突触和mTOR信号通路的调节有关。GO富集分析还显示，miR-615-3p的靶基因位于细胞核和细胞质中，参与转录和蛋白质磷酸化的调节，并与蛋白质结合、金属离子结合和转录因子活性有关。miR-615-3p的靶基因在Ras和FoxO信号通路的调节中起重要作用。总之，miR-4722-5p和miR-615-3p可能是AD早期诊断的潜在生物标志物。
