Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong, China.
Cell Biology Department, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
J Alzheimers Dis. 2021;82(1):169-183. doi: 10.3233/JAD-210068.
Alzheimer's disease (AD) is a chronic neurodegenerative disease that seriously impairs both cognitive and memory functions mainly in the elderly, and its incidence increases with age. Recent studies demonstrated that long noncoding RNAs (lncRNAs) play important roles in AD by acting as competing endogenous RNAs (ceRNAs).
In this study, we aimed to construct lncRNA-associated ceRNA regulatory networks composed of potential biomarkers in AD based on the ceRNA hypothesis.
A total of 20 genes (10 upregulated genes and 10 downregulated genes) were identified as the hub differentially expressed genes (DEGs). The functional enrichment analysis showed that the most significant pathways of DEGs involved include retrograde endocannabinoid signaling, synaptic vesicle circle, and AD. The upregulated hub genes were mainly enriched in the cytokine-cytokine receptor interaction pathway, whereas downregulated hub genes were involved in the neuroactive ligand-receptor interaction pathway. After convergent functional genomic (CFG) ranks and expression level analysis in different brain regions of hub genes, we found that CXCR4, GFAP, and GNG3 were significantly correlated with AD. We further identified crucial miRNAs and lncRNAs of targeted genes to construct lncRNA-associated ceRNA regulatory networks.
The results showed that two lncRNAs (NEAT1, MIAT), three miRNAs (hsa-miR-551a, hsa-miR-133b and hsa-miR-206), and two mRNA (CXCR4 and GNG3), which are highly related to AD, were preliminarily identified as potential AD biomarkers.
Our study provides new insights for understanding the pathogenic mechanism underlying AD, which may potentially contribute to the ceRNA mechanism in AD.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，主要影响老年人的认知和记忆功能，其发病率随年龄增长而增加。最近的研究表明，长链非编码 RNA（lncRNA）通过作为竞争性内源性 RNA（ceRNA）在 AD 中发挥重要作用。
基于 ceRNA 假说，本研究旨在构建由 AD 中潜在生物标志物组成的 lncRNA 相关 ceRNA 调控网络。
共鉴定出 20 个基因（10 个上调基因和 10 个下调基因）作为差异表达基因（DEG）的枢纽基因。功能富集分析表明，DEG 最显著的途径包括逆行内源性大麻素信号、突触小泡循环和 AD。上调的枢纽基因主要富集在细胞因子-细胞因子受体相互作用途径，而下调的枢纽基因则参与神经活性配体-受体相互作用途径。对枢纽基因在不同脑区的收敛功能基因组（CFG）排名和表达水平分析后，我们发现 CXCR4、GFAP 和 GNG3 与 AD 显著相关。我们进一步鉴定了靶向基因的关键 miRNA 和 lncRNA，以构建 lncRNA 相关 ceRNA 调控网络。
结果表明，两个 lncRNA（NEAT1、MIAT）、三个 miRNA（hsa-miR-551a、hsa-miR-133b 和 hsa-miR-206）和两个 mRNA（CXCR4 和 GNG3）与 AD 高度相关，初步被鉴定为潜在的 AD 生物标志物。
本研究为理解 AD 的发病机制提供了新的见解，可能有助于 AD 中的 ceRNA 机制。
