Differentially Expressed Circular Non-coding RNAs in Atherosclerotic Aortic Vessels and Their Potential Functions in Endothelial Injury.
Differentially Expressed Circular Non-coding RNAs in Atherosclerotic Aortic Vessels and Their Potential Functions in Endothelial Injury.
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动脉粥样硬化主动脉血管中差异表达的环状非编码RNA及其在内皮损伤中的潜在功能
DOI：
10.3389/fcvm.2021.657544
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发表时间：
2021
影响因子：
3.6
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li H;Liu X;Sun N;Wang T;Zhu J;Yang S;Song X;Wang R;Wang X;Zhao Y;Zhang Y
背景：环状非编码RNA（circular non-coding RNA，circRNA）具有多种生物学功能。然而，circRNA在动脉粥样硬化（AS）和血管内皮损伤中的表达谱和潜在作用尚未完全阐明。本研究旨在鉴定动脉粥样硬化血管中差异表达的circRNA，并预测其在内皮损伤中的潜在功能。方法：采用高脂饲料喂养ApoE-/-小鼠12周，建立AS模型。采用H&E染色、Masson染色和免疫组化方法评价动脉粥样硬化斑块;采用Arraystar Circular RNA Microarray检测差异表达的circRNA，并通过RT-PCR验证;采用米兰达、Tarbase、Targetscan预测circRNA的潜在靶基因，并通过RT-PCR验证其表达变化;采用Targetscan预测circRNA的潜在靶基因，并通过Western blot验证其表达变化;通过基因富集分析预测它们可能注释或调节的信号通路及其在血管内皮损伤中的潜在功能。结果：在AS主动脉血管中，有52个circRNA表达上调2倍以上，47个circRNA表达下调1.5倍以上。Mmmu_circRNA_36781和37699在AS主动脉血管和H2 O2处理的小鼠主动脉内皮细胞（MAECs）中均上调。miR-30 d-3 p和miR-140- 3 p（circRNA_37699和circRNA_36781的靶microRNA）在AS血管和H2 O2处理的MAEC中的表达均下调。与此相反，miR-140- 3 p和miR-30 d-3 p的潜在靶基因MKK 6和TP 53 RK在AS主动脉根部和H2 O2处理的MAEC中均上调。此外，基因富集分析显示MAPK和PI 3 K-AKT信号通路是动脉粥样硬化中差异表达的circRNA最有可能调控的信号通路。结论：Mmu_circRNA_36781（circRNA ABCA 1）和37699（circRNA KHDRBS 1）在AS主动脉血管和H2 O2处理的MAEC中显著上调。它们通过靶向miR-30 d-3 p-TP 53 RK和miR-140- 3 p-MKK 6轴及其下游信号通路对动脉粥样硬化和血管内皮损伤具有潜在的调节作用。
Background: Circular non-coding RNA (circRNA) has a variety of biological functions. However, the expression profile and potential effects of circRNA on atherosclerosis (AS) and vascular endothelial injury have not been fully elucidated. This study aims to identify the differentially expressed circRNAs in atherosclerotic aortic vessels and predict their potential functions in endothelial injury. Method: ApoE-/- mice were fed with high-fat diet for 12 weeks to induce AS. Atherosclerotic plaques were evaluated by H&E and Masson staining and immunohistochemistry; differentially expressed circRNAs were detected by Arraystar Circular RNA Microarray and verified by RT-PCR; the potential target mircoRNAs of circRNAs were predicted by miRanda, Tarbase, Targetscan and their expression changes were verified by RT-PCR; the potential target genes of mircoRNAs were predicted by Targetscan and verified by Western blot; the signaling pathways that they might annotate or regulate and their potential functions in vascular endothelial injury were predicted by gene enrichment analysis. Results: Fifty two circRNAs were up-regulated more than twice and 47 circRNAs were down-regulated more than 1.5 times in AS aortic vessels. Mmmu_circRNA_36781 and 37699 were up-regulated both in AS aortic vessels and H2O2-treated mouse aortic endothelial cells (MAECs). The expression of miR-30d-3p and miR-140-3p, the target microRNA of circRNA_37699 and circRNA_36781, were downregulated both in AS vessels and H2O2-treated MAECs. On the contrary, MKK6 and TP53RK, the potential target gene of miR-140-3p and miR-30d-3p, were upregulated both in AS aortic roots and H2O2-treated MAECs. Besides, gene enrichment analysis showed that MAPK and PI3K-AKT signaling pathway were the most potential signaling pathways regulated by the differentially expressed circRNAs in atherosclerosis. Conclusions: Mmu_circRNA_36781 (circRNA ABCA1) and 37699 (circRNA KHDRBS1) were significantly up-regulated in AS aortic vessels and H2O2-treated MAECs. They have potential regulatory effects on atherosclerosis and vascular endothelial injury by targeting miR-30d-3p-TP53RK and miR-140-3p-MKK6 axis and their downstream signaling pathways.
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circRNA生物合成的调控
影响因子：
4.1
作者：
Chen, Ling-Ling;Yang, Li
通讯作者：
Yang, Li
影响因子：
2.9
作者：
Bolha L;Ravnik-Glavač M;Glavač D
通讯作者：
Glavač D
DOI：
10.1083/jcb.201504007
发表时间：
2015-09-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Grimsey NJ;Aguilar B;Smith TH;Le P;Soohoo AL;Puthenveedu MA;Nizet V;Trejo J
通讯作者：
Trejo J
VNN1 促进高脂肪/高胆固醇饮食的 apoE(-/-) 小鼠动脉粥样硬化进展
影响因子：
6.5
作者：
Hu YW;Wu SG;Zhao JJ;Ma X;Lu JB;Xiu JC;Zhang Y;Huang C;Qiu YR;Sha YH;Gao JJ;Wang YC;Li SF;Zhao JY;Zheng L;Wang Q
通讯作者：
Wang Q
影响因子：
20.1
作者：
Gimbrone MA Jr;García-Cardeña G
通讯作者：
García-Cardeña G