Li Xiaokai, Feng Siyuan, Luo Yi, Long Keren, Lin Zhenghao, Ma Jideng, Jiang Anan, Jin Long, Tang Qianzi, Li Mingzhou, Wang Xun
Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China.
In Vitro Cell Dev Biol Anim. 2018 Feb;54(2):99-110. doi: 10.1007/s11626-017-0225-3. Epub 2018 Jan 10.
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.
巨噬细胞源性泡沫细胞是动脉粥样硬化的标志之一，而微小RNA在泡沫细胞形成中发挥重要作用。为了探究微小RNA在泡沫细胞形成中的作用，我们通过高通量测序技术研究了泡沫细胞中的微小RNA表达谱。在RAW 264.7巨噬细胞和氧化型低密度脂蛋白诱导的泡沫细胞之间，共有84种微小RNA差异表达。其中30种微小RNA上调，54种微小RNA下调。基因本体论（GO）术语和京都基因与基因组百科全书（KEGG）通路分析显示，大多数差异表达微小RNA的靶基因主要富集于“细胞分化”、“内吞作用”、“丝裂原活化蛋白激酶（MAPK）信号通路”和“叉头框蛋白O（FoxO）信号通路”。一些差异表达微小RNA的靶基因富集于“胰岛素信号通路”、“河马信号通路”、“肿瘤坏死因子（TNF）信号通路”、“核因子κB（NF-κB）信号通路”和“细胞死亡”。通过生物信息学分析和双荧光素酶报告基因检测，我们发现miR-28a-5p和miR-30c-1-3p分别通过靶向LRAD3和LOX-1 mRNA的3'非翻译区（3'UTR）直接抑制LRAD3和LOX-1 mRNA表达。我们的研究表明，微小RNA广泛参与泡沫细胞的形成，并为进一步研究微小RNA在动脉粥样硬化中的作用提供了有价值的资源。
