雷公藤多苷治疗的Aβ诱导AD小鼠模型中lncRNA相关竞争性内源RNA调控网络
lncRNA-Associated Competitive Endogenous RNA Regulatory Network in an Aβ-Induced AD Mouse Model Treated with Tripterygium Glycoside.
作者信息
Tang Liang, Xiang Qin, Xiang Ju, Li Jianming
机构信息
Department of Basic Biology, Changsha Medical College, Changsha, People's Republic of China.
Department of Basic Biology, Wuzhou Medical College, Wuzhou, People's Republic of China.
出版信息
Neuropsychiatr Dis Treat. 2021 May 19;17:1531-1541. doi: 10.2147/NDT.S310271. eCollection 2021.
BACKGROUND
Tripterygium glycoside (TG) has been suggested to have protective effects on the diseases of the central nervous system including Alzheimer's disease (AD). The mechanisms involving lncRNA-associated competing endogenous RNAs (ceRNAs) were shown to play important roles in the development of AD. However, the ceRNA mechanism of TG in treating AD is still unknown. Thus, we aimed to explore the ceRNA mechanism in the treatment of AD with TG.
METHODS
A total of 32 C57BL/6J mice were administered 3 µL of Aβ (dual side, 1 mg/mL) by a single stereotactic injection in the brain to conduct AD mouse model. AD mouse models were randomly selected and divided into the AD+normal saline (NS) group (n=16) and the AD+TG group (n=16). The expression data of lncRNAs, mRNAs, and miRNAs in the hippocampus of mice from AD+NS group (n=3) and the AD+TG group (n=3) were obtained by microarray analysis. The MuTaME method was used to predict the ceRNA regulatory network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID database. A protein-protein interaction (PPI) network was constructed by using STRING software.
RESULTS
TG can significantly improve spatial memory and inhibit the production of p-tau in an Aβ-induced AD mouse model. A total of 661 differentially expressed lncRNAs, 503 mRNAs, and 13 miRNAs were identified. A ceRNA network involving the top 200 mRNA-miRNA-lncRNA pairs with 16 lncRNAs, 11 miRNAs, and 52 mRNAs was visualized. And a PPI network complex filtered 26 gene nodes in DEGs was predicted.
CONCLUSION
We have identified 503 DEGs, 661 DElncRNAs, and 13 DEmiRNAs during treatment with TG in Aβ-induced AD mouse model. A ceRNA network based on the DElncRNAs, DEmRNAs, and DEmiRNAs was conducted, which provided new insight into the lncRNA-mediated ceRNA regulatory mechanisms underlying the effects of TG in the treatment of AD.
背景
雷公藤多苷（TG）已被证明对包括阿尔茨海默病（AD）在内的中枢神经系统疾病具有保护作用。涉及长链非编码RNA相关竞争性内源RNA（ceRNA）的机制在AD的发展中起着重要作用。然而，TG治疗AD的ceRNA机制仍不清楚。因此，我们旨在探索TG治疗AD的ceRNA机制。
方法
通过在大脑中单次立体定向注射3 μL Aβ（双侧，1 mg/mL）对32只C57BL/6J小鼠进行AD小鼠模型构建。随机选取AD小鼠模型并分为AD+生理盐水（NS）组（n = 16）和AD+TG组（n = 16）。通过微阵列分析获得AD+NS组（n = 3）和AD+TG组（n = 3）小鼠海马中lncRNAs、mRNAs和miRNAs的表达数据。使用MuTaME方法预测ceRNA调控网络。使用DAVID数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析。使用STRING软件构建蛋白质-蛋白质相互作用（PPI）网络。
结果
在Aβ诱导的AD小鼠模型中，TG可显著改善空间记忆并抑制p-tau的产生。共鉴定出661个差异表达的lncRNAs、503个mRNAs和13个miRNAs。可视化了一个包含前200个mRNA-miRNA-lncRNA对的ceRNA网络，其中有16个lncRNAs、11个miRNAs和52个mRNAs。并且预测了一个在差异表达基因（DEGs）中筛选出26个基因节点的PPI网络复合体。
结论
在Aβ诱导的AD小鼠模型中使用TG治疗期间，我们鉴定出503个DEGs、661个DElncRNAs和13个DEmiRNAs。基于DElncRNAs、DEmRNAs和DEmiRNAs构建了一个ceRNA网络，这为TG治疗AD作用下lncRNA介导的ceRNA调控机制提供了新的见解。
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