The glial-specific hypermethylated 3′ untranslated region of histone deacetylase 1 may modulates several signal pathways in Alzheimer’s disease
The glial-specific hypermethylated 3′ untranslated region of histone deacetylase 1 may modulates several signal pathways in Alzheimer’s disease
复制标题
组蛋白脱乙酰酶 1 的神经胶质特异性 3-非翻译区可能调节阿尔茨海默病的多个信号通路
DOI：
10.1016/j.lfs.2020.118760
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Songran Yang
中科院分区：
文献类型：
--
作者：
Lei Lv;Dingwen Zhang;Ping Hua;Songran Yang
目的表观遗传调控在阿尔茨海默病（Alzheimer's disease，AD）的发病过程中起重要作用。在这里，我们确定了差异甲基化探针（DMPs），并调查其在AD中的潜在机制作用。主要方法DMPs通过生物信息学分析GSE 66351，这是由106个AD样本和84个对照样本来自三个不同的大脑区域。基于包括45个对照样品和58个AD样品的GSE 5281分析差异表达基因（DEG）。基因本体论（GO）、基因集富集分析（GSEA）和蛋白质-蛋白质相互作用（PPI）用于识别途径和中心基因。关键发现我们在枕叶皮质胶质细胞中发现了9007个DMP，在OC神经元中发现了1527个DMP，在颞叶皮质中发现了100个DMP，在额叶皮质中发现了194个DMP。在初级视皮层中鉴定出74个DEG，其中67个下调，7个上调。颞内侧回上调482例，下调697例。在上级额回中，687个上调，85个下调。GO和PPI显示，涉及上皮细胞分化，细胞对脂质的反应，转录辅阻遏物的活动，凋亡和器官生长的途径是由组蛋白去乙酰化酶1（HDAC 1）调节，并与AD相关。此外，GSEA结果表明，转化生长因子β信号通路在某些脑区明显富集，HDAC 1在该通路中起重要作用。此外，我们还推测HDAC 1通过调节组蛋白去乙酰化而触发与许多不同生物过程和功能相关的信号通路。
AimsEpigenetic regulation plays an important role in the progression of Alzheimer's disease (AD). Here, we identified differential methylation probes (DMP) and investigated their potential mechanistic roles in AD.Main methodsDMPs were identified via bioinformatic analysis of GSE66351, which was made up with 106 AD samples and 84 control samples derived from three separate brain regions. Differentially expressed genes (DEGs) were analyzed based on GSE5281 comprising 45 control samples and 58 AD samples. Gene ontology (GO), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) were used to identify pathways and hub genes.Key findingsWe found 9007 DMPs in Occipital Cortex glia, 1527 in OC neurons, 100 in Temporal Cortex, and 194 in Frontal Cortex. 74 DEGs were identified in Primary Visual Cortex, 67 of which were downregulated while seven upregulated. 482 were upregulated and 697 downregulated in medial temporal gyrus. In superior frontal gyrus, 687 were upregulated and 85 downregulated. GO and PPI revealed that pathways involving epithelial-cell differentiation, cellular responses to lipids, transcription corepressor activities, apoptotic and organ growth were modulated by histone deacetylase 1 (HDAC1) and associated with AD. Additionally, GSEA illustrated that the transforming growth factor beta signaling pathway was significantly enriched in some brain regions and HDAC1 played an important role in this pathway.SignificanceWe found the glial-specific 3′UTR of HDAC1 was hypermethylated and HDAC1 was overexpressed in AD patients. Moreover, we also speculate that HDAC1 triggered signaling pathways linked to many different biological processes and functions via the regulation of histone deacetylation.