Identification of age- and gender-associated long noncoding RNAs in the human brain with Alzheimer's disease
Identification of age- and gender-associated long noncoding RNAs in the human brain with Alzheimer's disease
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DOI：
10.1016/j.neurobiolaging.2019.05.023
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发表时间：
2019-09-01
影响因子：
4.2
通讯作者：
Hu, Guoku
中科院分区：
文献类型：
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作者：
Cao, Mei;Li, Huaqing;Hu, Guoku
阿尔茨海默病（AD）是一种与年龄和性别相关的脑部疾病。长链非编码RNA（lncRNA）已经成为脑发育、稳态和病理的关键调节因子。在这里，我们使用基因阵列数据集和生物信息学分析，以确定差异表达的年龄和性别相关的lncRNA在人类AD大脑。我们发现，16个与年龄相关和13个与性别相关的lncRNA在AD脑中表达失调。值得注意的是，与年龄相关的IncRNAs-SNHG 19和LINC 00672-的表达分别与AD的Braak分期显著正相关和负相关，而与性别相关的IncRNAs-RNF 144 A-AS 1、LY 86-AS 1和LINC 00639-的表达与AD的Braak分期呈负相关。功能分析表明，参与神经退行性疾病，突触囊泡周期和内吞作用的途径在年龄和性别相关的lncRNA相关基因中过度表达。年龄和性别相关的lncRNA及其在人类AD大脑中的差异表达的鉴定为进一步的实验验证和机制研究提供了潜在的靶点，这反过来又为开发针对AD患者的年龄和性别特异性预防和预防性治疗选择铺平了道路。(C)2019爱思唯尔公司All rights reserved.
Alzheimer's disease (AD) is an age- and gender-associated brain disorder. Long noncoding RNAs (lncRNAs) have emerged as key regulators of brain development, homeostasis, and pathologies. Here, we used gene array data sets and bioinformatics analysis to identify differentially expressed age- and gender-associated lncRNAs in human AD brains. We found that the expressions of 16 age-associated and 13 gender-associated lncRNAs were dys regulated in AD brains. Notably, the expressions of age-associated IncRNAs-SNHG19 and LINC00672-were significantly correlated with Braak stage of AD, positively and negatively, respectively, whereas the expressions of gender-associated lncRNAs-RNF144A-AS1, LY86-AS1, and LINC00639-were negatively correlated with Braak stage of AD. Functional analysis suggests that the pathways involved in neurodegenerative diseases, synaptic vesicle cycle, and endocytosis were overly represented within ageand gender-associated lncRNA-correlating genes. The identification of age- and gender-associated lncRNAs and their differential expressions in the human AD brain provide potential targets for further experimental validation and mechanistic investigation, which could, in turn, pave the way for developing age- and gender-specific prevention and adjunctive therapeutic options for patients with AD. (C) 2019 Elsevier Inc. All rights reserved.