Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Department of Neurology, The Affiliated Hospital of Jining Medical University, Jining, 272000, China.
Metab Brain Dis. 2020 Jan;35(1):201-213. doi: 10.1007/s11011-019-00497-y. Epub 2019 Dec 13.
Expression of circular RNA (circRNA), a class of noncoding RNAs that regulates gene expression, is altered in Alzheimer's disease. This study profiled differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from five patients with Alzheimer's disease compared to healthy controls using circRNA microarrays. We identified a total of 4060 differentially expressed circRNAs (1990 upregulated and 2070 downregulated) in Alzheimer's disease patients. Among these circRNAs, 10 randomly selected circRNAs were verified using qRT-PCR. The top 10 upregulated and downregulated circRNAs were used to predict their target miRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these differentially expressed circRNAs were strongly associated with inflammation, metabolism, and immune responses, which are all risk factors for Alzheimer's disease. The circRNA-miRNA-mRNA network was most involved in the MAPK, mTOR, AMPK, and WNT signaling pathways in Alzheimer's disease. In conclusion, the current study demonstrated the importance of circRNAs in Alzheimer's disease development. Future studies will evaluate some of these circRNAs as biomarkers for early disease detection and to develop therapeutic strategies to clinically control Alzheimer's disease progression.
环状 RNA（circRNA）的表达发生改变，这是一类调节基因表达的非编码 RNA，在阿尔茨海默病中。本研究采用 circRNA 微阵列比较了 5 例阿尔茨海默病患者与健康对照者外周血单个核细胞（PBMC）中差异表达的 circRNAs。我们在阿尔茨海默病患者中总共鉴定出 4060 个差异表达的 circRNAs（1990 个上调和 2070 个下调）。在这些 circRNAs 中，使用 qRT-PCR 验证了 10 个随机选择的 circRNAs。使用 top10 个上调和下调的 circRNAs 来预测其靶 miRNAs。基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析表明，这些差异表达的 circRNAs 与炎症、代谢和免疫反应强烈相关，这些都是阿尔茨海默病的风险因素。circRNA-miRNA-mRNA 网络在阿尔茨海默病中最涉及 MAPK、mTOR、AMPK 和 WNT 信号通路。总之，本研究表明 circRNAs 在阿尔茨海默病发展中的重要性。未来的研究将评估其中一些 circRNAs 作为早期疾病检测的生物标志物，并开发治疗策略来临床控制阿尔茨海默病的进展。
