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CLC number: Q291

On-line Access: 2019-09-06

Received: 2018-12-18

Revision Accepted: 2019-05-14

Crosschecked: 2019-08-14

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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.10 P.803-815

10.1631/jzus.B1800631


Analysis of cardiovascular disease-related NF-κB-regulated genes and microRNAs in TNFα-treated primary mouse vascular endothelial cells


Author(s):  Hui Zhu, Yun Li, Mao-Xian Wang, Ju-Hong Wang, Wen-Xin Du, Fei Zhou

Affiliation(s):  School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou 521041, China; more

Corresponding email(s):   zhoufei1200@163.com

Key Words:  Cardiovascular disease, Nuclear factor-κ, B (NF-κ, B), MicroRNA, Endothelial cell


Hui Zhu, Yun Li, Mao-Xian Wang, Ju-Hong Wang, Wen-Xin Du, Fei Zhou. Analysis of cardiovascular disease-related NF-κB-regulated genes and microRNAs in TNFα-treated primary mouse vascular endothelial cells[J]. Journal of Zhejiang University Science B, 2019, 20(10): 803-815.

@article{title="Analysis of cardiovascular disease-related NF-κB-regulated genes and microRNAs in TNFα-treated primary mouse vascular endothelial cells",
author="Hui Zhu, Yun Li, Mao-Xian Wang, Ju-Hong Wang, Wen-Xin Du, Fei Zhou",
journal="Journal of Zhejiang University Science B",
volume="20",
number="10",
pages="803-815",
year="2019",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1800631"
}

%0 Journal Article
%T Analysis of cardiovascular disease-related NF-κB-regulated genes and microRNAs in TNFα-treated primary mouse vascular endothelial cells
%A Hui Zhu
%A Yun Li
%A Mao-Xian Wang
%A Ju-Hong Wang
%A Wen-Xin Du
%A Fei Zhou
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 10
%P 803-815
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1800631

TY - JOUR
T1 - Analysis of cardiovascular disease-related NF-κB-regulated genes and microRNAs in TNFα-treated primary mouse vascular endothelial cells
A1 - Hui Zhu
A1 - Yun Li
A1 - Mao-Xian Wang
A1 - Ju-Hong Wang
A1 - Wen-Xin Du
A1 - Fei Zhou
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 10
SP - 803
EP - 815
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1800631


Abstract: 
Activated nuclear factor-κ;b (NF-κ;b) plays an important role in the development of cardiovascular disease (CVD) through its regulated genes and microRNAs (miRNAs). However, the gene regulation profile remains unclear. In this study, primary mouse vascular endothelial cells (pMVECs) were employed to detect CVD-related NF-κB-regulated genes and miRNAs. Genechip assay identified 77 NF-κB-regulated genes, including 45 upregulated and 32 downregulated genes, in tumor necrosis factor α (TNFα)-treated pMVECs. Ten of these genes were also found to be regulated by NF-κB in TNFα-treated HeLa cells. Quantitative real-time PCR (qRT-PCR) assay confirmed the up-regulation of Egr1, Tnf, and Btg2 by NF-κB in the TNFα-treated pMVECs. The functional annotation revealed that many NF-κB-regulated genes identified in pMVECs were clustered into classical NF-κB-involved biological processes. Genechip assay also identified 26 NF-κB-regulated miRNAs, of which 21 were upregulated and 5 downregulated, in the TNFα-treated pMVECs. Further analysis showed that nine of the identified genes are regulated by seven of these miRNAs. Finally, among the identified NF-κB-regulated genes and miRNAs, 5 genes and 12 miRNAs were associated with CVD by miRWalk and genetic association database analysis. Taken together, these findings show an intricate gene regulation network raised by NF-κB in TNFα-treated pMVECs. The network provides new insights for understanding the molecular mechanism underlying the progression of CVD.

基于TNFα处理的小鼠原代血管内皮细胞鉴定心血管疾病相关的NF-κB调控的基因和microRNA

目的:鉴定与心血管疾病相关的核因子κB(NF-κB)调控的基因和小RNA(microRNA),探讨疾病发生发展的机制.
创新点:构建心血管疾病相关的NF-κB调控网络.
方法:基于NF-κB转录活性差异的小鼠原代血管内皮细胞模型,采用基因芯片(Genechip)检测NF-κB调控的基因和microRNA.再通过实时荧光定量聚合酶链反应(qRT-PCR)和生物信息学方法进行差异基因和microRNA的筛选、验证、功能注释,从而发现与心血管疾病相关的NF-κB调控的基因和microRNA.
结论:在肿瘤坏死因子α(TNFα)处理的小鼠原代血管内皮细胞中:NF-κB调控77个基因,其中45个基因上调,32个基因下调.NF-κB还在TNFα处理的HeLa细胞中调控其中10个基因.通过qRT-PCR验证了NF-κB上调Egr1TnfBtg2的表达.基因功能注释表明,许多NF-κB调节的基因聚类到经典的NF-κB参与的生物学过程.在TNFα处理的小鼠原代血管内皮细胞中还发现:NF-κB调控26个microRNA,其中21个上调,5个下调.进一步研究发现,7个NF-κB调控的microRNA还可能调控9个NF-κB调控的基因.最后通过检索数据库发现,5个NF-κB调控的基因和12个NF-κB调控的microRNA与心血管疾病相关.因此,本研究提升了对心血管疾病进展分子机制的理解.

关键词:心血管疾病;核因子κB;小RNA;内皮细胞

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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