Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, 110001 Liaoning, China.
Cancer Systems Biology Center, The China-Japan Union Hospital, Jilin University, Changchun, 130033 Jilin, China.
Oxid Med Cell Longev. 2021 Apr 19;2021:5555634. doi: 10.1155/2021/5555634. eCollection 2021.
The objective of this study was to investigate the potential molecular mechanisms of ATPase H transporting V1 subunit A (ATP6V1A) underlying Alzheimer's disease (AD).
Microarray expression data of human temporal cortex samples from the GSE118553 dataset were profiled to screen for differentially expressed genes (DEGs) between AD/control and ATP6V1A-low/high groups. Correlations of coexpression modules with AD and ATP6V1A were assessed by weight gene correlation network analysis (WGCNA). DEGs strongly interacting with ATP6V1A were extracted to construct global regulatory network. Further cross-talking pathways of ATP6V1A were identified by functional enrichment analysis. Diagnostic performance of ATP6V1A in AD prediction was evaluated using area under the curve (AUC) analysis.
The mean expression of ATP6V1A was significantly downregulated in AD compared with nondementia controls. A total of 1,364 DEGs were overlapped from AD/control and ATP6V1A-low/high groups. Based on these DEGs, four coexpression modules were predicted by WGCNA. The blue, brown, and turquoise modules were significantly correlated with AD and low ATP6V1A, whose DEGs were enriched in phagosome, oxidative phosphorylation, synaptic vesicle cycle, focal adhesion, and gamma-aminobutyric acidergic (GABAergic) synapse. Global regulatory network was constructed to identify the cross-talking pathways of ATP6V1A, such as synaptic vesicle cycle, phagosome, and oxidative phosphorylation. According to the AUC value of 74.2%, low ATP6V1A expression accurately predicted the occurrence of AD.
Our findings highlighted the pleiotropic roles of low ATP6V1A in AD pathogenesis, possibly mediated by synaptic vesicle cycle, phagosome, and oxidative phosphorylation.
本研究旨在探讨 ATP 酶 H 转运 V1 亚基 A（ATP6V1A）在阿尔茨海默病（AD）中的潜在分子机制。
从 GSE118553 数据集的人类颞叶皮质样本中进行微阵列表达数据分析，以筛选 AD/对照和 ATP6V1A-低/高组之间差异表达基因（DEG）。通过加权基因相关网络分析（WGCNA）评估与 AD 和 ATP6V1A 相关的共表达模块的相关性。提取与 ATP6V1A 强烈相互作用的 DEG 以构建全局调控网络。通过功能富集分析进一步鉴定 ATP6V1A 的交叉对话途径。使用曲线下面积（AUC）分析评估 ATP6V1A 在 AD 预测中的诊断性能。
与非痴呆对照相比，AD 中 ATP6V1A 的平均表达明显下调。AD/对照和 ATP6V1A-低/高组重叠的共有 1364 个 DEG。基于这些 DEG，WGCNA 预测了四个共表达模块。蓝色、棕色和绿松石色模块与 AD 和低 ATP6V1A 显著相关，其 DEG 富集在吞噬体、氧化磷酸化、突触小泡循环、黏着斑和γ-氨基丁酸能（GABAergic）突触。构建全局调控网络以鉴定 ATP6V1A 的交叉对话途径，如突触小泡循环、吞噬体和氧化磷酸化。根据 74.2%的 AUC 值，低 ATP6V1A 表达准确预测了 AD 的发生。
我们的研究结果强调了低 ATP6V1A 在 AD 发病机制中的多效性作用，可能通过突触小泡循环、吞噬体和氧化磷酸化介导。
