家族性高胆固醇血症HDL-miRNAs调节血单核细胞功能机制  

Mechanism of HDL-miRNAs modulating the function of the peripheral blood monocyte in patients with familial hypercholesterolemia

作　　者：丁毅 杜芬[1] 喻红[1] DING Yi;DU Fen;YU Hong(Basic Medical Sehool,Wuhan university,Wuhan 433071,Hubei,China;Ultrasoun of clinical medicine Shanghai East Hospital,Shanghai 200120,China)

机构地区：[1]武汉大学基础医学院,湖北武汉433071 [2]上海市东方医院医学超声科,上海200120

出　　处：《生物资源》2020年第3期335-341,共7页Biotic Resources

基　　金：国家自然科学基金面上项目(81670423)。

摘　　要：本研究通过生物信息学方法分析家族性高胆固醇血症患者外周血单核细胞差异表达基因、HDL载体差异表达miRNA及其生物学功能,研究差异HDL-miRNA与单核细胞差异基因的相关性,探讨HDL-miRNA调控外周血单核细胞功能机制,寻找动脉粥样硬化防治新靶点。运用R语言分析GEO数据库共享平台家族性高胆固醇血症外周血单核细胞基因及HDL-miRNA探针芯片得到差异基因及差异miRNA,利用miRwalk2. 0预测miRNA靶基因,并利用STRING进行蛋白互作分析,构建差异miRNA与差异基因之间的调控网络。运用GO及KEGG分析研究基因功能。利用GEO数据(GSE6054)筛选出834个差异表达基因,利用GEO数据(GSE25108)筛选出HDL上差异miRNA28个。交叉匹配得到由19个差异miRNA和56个差异基因组配对的74对miRNA-靶基因。GO富集分析56个差异基因主要富集于肾上腺素受体信号等分子功能。KEGG分析56个差异基因主要富集于造血谱系通路上。家族性高胆固醇血症差异HDL-miRNA与外周血单核细胞差异mRNA具有相关性,HDL-miRNA有通过调控血单核细胞功能的可能性,可能参与高胆固醇血症导致动脉粥样硬化过程。To explore the effect of HDL-miRNA on peripheral blood monocytes in the process of atherosclerosis by bioinformatics,we analyzed the biological functions of the differential expression of genes(DGEs)in peripheral blood monocytes and the differential expression of HDL-miRNAs(DEMs)in patients with familial hypercholesterolemia.The data of gene and miRNA related familial hypercholesterolemia was obtained from GEO database.DGEs and DEMs were analyzed by R language.The miRwalk2.0 online tool was used to predict miRNA target genes and protein interaction analysis was performed by STRING to obtain the regulatory network between DGEs and DEMs.GO and KEGG analyzed the function of related genes.GEO data(GSE6054)was used to screen 834 DEGs and GEO data(GSE25108)was used to screen 28 DEMs on HDL in patients with hypercholesterolemia.Cross-matching was performed and obtain74 pairs of miRNA gene pairs in 19 DEMs and 56 DGEs.GO analysis showed that the 56 DGEs were mainly concentrated in the molecular functions of adrenergic receptor signal.KEGG analysis showed that 56 differentially expressed genes mainly enriched in the hematopoietic cell lineage pathway.The analysis of the DGEs in peripheral blood monocytes and HDL-DEMs in patients with familial hypercholesterolemia based on bioinformatics provides a new perspective for the study of atherosclerosis,providing a new sight in screening diagnostic markers and drug therapeutic targets of atherosclerosis.

关 键 词：家族性高胆固醇血症 HDL miRNA 外周血单核细胞 生物信息学分析 动脉粥样硬化 

分 类 号：R318.04[医药卫生—生物医学工程]