Department of Medical Biology, Health Sciences Institution, Dokuz Eylul University, İnciraltı, İzmir, Turkey.
Department of Medical Biology, Faculty of Medicine, Pamukkale University, Denizli, Turkey.
Mol Neurobiol. 2020 Dec;57(12):5352-5361. doi: 10.1007/s12035-020-02106-x. Epub 2020 Sep 3.
Long non-coding RNAs (lncRNAs) are involved in many neurological conditions, and neurodegenerative disorders including Alzheimer's disease (AD) regulate gene expression at transcriptional, post-transcriptional, and epigenetic levels. However, the roles of lncRNAs in the pathogenesis of AD remain unclear. In this study, we aimed to determine the expression of lncRNAs and also mRNAs in AD which may alter expression and contribute to the pathogenesis of the disease. Peripheral blood samples were obtained from patients admitted to the Neurology Department of Pamukkale University Medical Faculty (23 patients with AD, 33 control groups). Total RNA obtained from peripheral blood mononuclear cells (PBMC) of subjects with probable AD (n = 4) and healthy control groups (n = 4) was examined to determine the altered expression of lncRNAs and mRNAs in AD were evaluated by microarray analysis. Five lncRNAs with the highest end-to-end fold change (fc ≥ 2.0, p < 0.05) were identified and confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). In our study, the profiles of lncRNAs and mRNAs that may be associated with Alzheimer's disease were determined. A total of 14 lncRNAs and 35 mRNAs were determined as upregulated, and 20 lncRNAs and 73 mRNAs determined as downregulated as a result of microarray analysis in patients with AD compared with control groups (fold change ≥ 2.0, p < 0.05). From lncRNAs, expression of lncRNA TTC39C-AS1, lnc-AL445989.1-2, LINC01420, lnc-CSTB-1, and LOC401557 was confirmed by qRT-PCR. When assessed by KEGG analysis of AD PBMC lncRNA and mRNA profiles, TNF signaling pathway, PI3K/AKT, Ras, and MAPK pathways; glutamatergic, dopaminergic, and cholinergic synapses; GABA, and neurotrophin signaling pathways are found to be significant. This is the first known study to investigate lncRNA profiles in AD PBMCs. We think that these results may open a door to the understanding of AD pathogenesis targeted by lncRNAs.
长链非编码 RNA（lncRNAs）参与许多神经疾病，包括阿尔茨海默病（AD）在内的神经退行性疾病在转录、转录后和表观遗传水平上调节基因表达。然而，lncRNAs 在 AD 发病机制中的作用尚不清楚。在这项研究中，我们旨在确定 AD 中 lncRNAs 和 mRNAs 的表达情况，这些表达情况可能会改变并有助于疾病的发病机制。从 Pamukkale 大学医学院神经内科收治的患者（23 例 AD 患者，33 例对照组）中获得外周血样本。从可能患有 AD（n = 4）和健康对照组（n = 4）的外周血单个核细胞（PBMC）中获得总 RNA，通过微阵列分析评估 AD 中 lncRNAs 和 mRNAs 表达的改变。通过微阵列分析确定了 5 个具有最高末端到末端折叠变化（fc≥2.0，p＜0.05）的 lncRNAs，并通过实时定量聚合酶链反应（qRT-PCR）进行了验证。在本研究中，确定了可能与阿尔茨海默病相关的 lncRNAs 和 mRNAs 的图谱。与对照组相比，AD 患者的 lncRNA 和 mRNAs 表达谱分析确定了 14 个 lncRNAs 和 35 个 mRNAs 上调，20 个 lncRNAs 和 73 个 mRNAs 下调（fold change≥2.0，p＜0.05）。从 lncRNAs 中，通过 qRT-PCR 验证了 lncRNA TTC39C-AS1、lnc-AL445989.1-2、LINC01420、lnc-CSTB-1 和 LOC401557 的表达。通过 AD PBMC lncRNA 和 mRNA 图谱的 KEGG 分析评估，发现 TNF 信号通路、PI3K/AKT、Ras 和 MAPK 途径；谷氨酸能、多巴胺能和胆碱能突触；GABA 和神经营养因子信号通路具有显著性。这是第一项研究 AD PBMC 中 lncRNA 图谱的研究。我们认为，这些结果可能为理解 lncRNA 靶向的 AD 发病机制开辟了一扇大门。
