Abstract
Macrophage-derived foam cells were one of the hallmarks of atherosclerosis, and microRNAs played an important role in the formation of foam cells. In order to explore the roles of miRNA in the formation of foam cells, we investigated miRNA expression profiles in foam cells through high-throughput sequencing technology. A total of 84 miRNAs were differentially expressed between RAW 264.7 macrophages and foam cells induced by ox-LDL. Thirty miRNAs were upregulated and 54 miRNAs were downregulated. GO terms and KEGG pathways analysis revealed that the target genes of most of DE miRNAs were mainly enriched in “cell differentiation,” “endocytosis,” “MAPK signaling pathway,” and “FoxO signaling pathway.” The target genes of some DE miRNAs were enriched in “Insulin signaling pathway,” “Hippo signaling pathway,” “TNF signaling pathway,” “NF-kappa B signaling pathway,” and “cell death.” Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-28a-5p and miR-30c-1-3p directly inhibited LRAD3 and LOX-1 mRNA expression through targeting the 3’UTR of LRAD3 and LOX-1 mRNA, respectively. Our study indicates that miRNAs are extensively involved in the formation of foam cells, and provides a valuable resource for further study the role of miRNAs in atherosclerosis.
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Funding
The study was funded by the National Natural Science Foundation of China (31522055, 31530073 and 31472081), the Project of Sichuan Education Department (15ZA0008), the Application Basic Research Plan Project of Sichuan Province (2016JY0167), the National Program for Support of Top-notch Young Professionals, the Program for Innovative Research Team of Sichuan Province (2015TD0012), and the Science & Technology Support Program of Sichuan (2016NYZ0042).
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Xiaokai Li, Yi Luo, Mingzhou Li, and Xun Wang conceived and designed the experiments. Xiaokai Li, Yi Luo, and Zhenghao Lin performed the experiments. Siyuan Feng, Xiaokai Li, and Keren Long analyzed the data. Mingzhou Li and Xun Wang contributed reagents/materials. Xun Wang, Jideng Ma, Anan Jiang, Long Jin, and Qianzi Tang analyzed all of the experiments. Xiaokai Li and Xun Wang wrote the paper. Xun Wang and Mingzhou Li revised the paper.
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Li, X., Feng, S., Luo, Y. et al. Expression profiles of microRNAs in oxidized low-density lipoprotein-stimulated RAW 264.7 cells. In Vitro Cell.Dev.Biol.-Animal 54, 99–110 (2018). https://doi.org/10.1007/s11626-017-0225-3
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DOI: https://doi.org/10.1007/s11626-017-0225-3