lncRNA MRAK048635P1对血管平滑肌细胞miRNA的调控作用  

Regulation of LncRNA MRAK048635P1 on MiRNAs in Vascular Smooth Muscle Cells

作　　者：方根强[1] 祁佳[2] 黄黎亚[1] 赵仙先 陈书艳[1] Fang Genqiang;Qi Jia;Huang Liya(Department of Geriatric Medicine,Xinhua Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院老年医学科,200092 [2]上海交通大学医学院附属新华医院药学部,200092 [3]中国人民解放军海军军医大学附属长海医院心血管内科,上海200433

出　　处：《医学研究杂志》2020年第5期58-64,共7页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81570208)。

摘　　要：目的旨在预测VSMC细胞中MRAK048635P1参与调控的miRNAs并对其靶基因进行系统的生物学分析。方法利用特异性siRNA敲减来自正常大鼠胸主动脉VSMC中的MRAK048635P1基因。整体层次聚类分析用于判断各组中差异表达的miRNAs。应用miRanda、PITA和RNAhybrid预测差异表达的miRNAs的靶基因并取其交集作为分析的基因集合,分别进行gene ontology(GO)中的细胞组分(cellular component,CC)、分子功能(molecular function,MF)和生物学过程(biological process,BP)分析。最后,对差异表达的miRNAs的靶基因进行kyoto encyclopedia of genes and genomes(KEGG)生物通路富集分析。结果siRNA介导VSMC细胞MRAK048635P1下调后,共有12个差异表达的miRNAs,其中上调和下调的miRNAs个数分别为5和7。差异表达的miRNAs的靶基因共5066个。GO富集分析发现其中的302个基因主要富集于VSMC分化(如G protein-coupled estrogen receptor 1,Gper1),血管内皮迁移的负调控、心血管系统发育、信号受体活性、核染色质和蛋白结合以及免疫应答等。KEGG富集发现这些靶基因显著富集于轴突导向、昼夜节律、N-糖基生物合成、内吞蛋白加工、内质网矿物吸收、鞘脂代谢和核糖体生物合成等相关通路(P<0.05)。结论在VSMC中,MRAK048635P1可能通过与多种miRNAs相互作用而参与相关靶基因的调控,对于MRAK048635P1的深入研究有助于揭示VSMC在高血压病中的作用机制。Objective To predict the target genes in differentially expressed miRNAs and their function after down-regulation of MRAK048635P1 in VSMC cells.Methods Specific siRNA was performed to knockdown MRAK048635P1 in VSMC,isolated from thoracic aorta of rats.Global hierarchical cluster analysis was used to determine the differential expression of miRNAs in each group.The target genes of differentially expressed miRNAs were predicted by miRanda,PITA and RNAhybrid.The molecular function and biological process in GO and the enrichment of KEGG pathway were analyzed respectively.Results After down-regulation of MRAK048635P1,12 miRNAs were differentially expressed.The number of up-regulated and down-regulated miRNAs was 5 and 7,respectively.The target genes of differentially expressed miRNAs were 5066.GO enrichment analysis showed that 302 of these genes were mainly involved in VSMC differentiation,negative regulation of vascular endothelial migration,cardiovascular system development,signal receptor activity,nuclear chromatin and protein binding,and immune response.KEGG enrichment revealed that these target genes were significantly enriched in axon guidance,circadian rhythm,N-glycan biosynthesis,endocytosis,protein processing in endoplasmic reticulum,mineral absorption,sphingolipid metabolism,lysosome,ribosome biogenesis in eukaryotes,herpes simplex infection,terpenoid backbone biosynthesis,renin-angiotensin system,vitamin digestion and absorption,neuroactive ligand-receptor interaction,inflammatory mediator regulation of TRP channels,caffeine metabolism,glycolysis/gluconeogenesis,fructose and mannose metabolism,fat digestion and absorption and rheumatoid arthritis(P<0.05).Conclusion MRAK048635P1 may be involved in the regulation of target genes by interacting with a variety of miRNAs,and plays an important role in various physiological and pathological processes of the organism.It is a valuable biological target for the study of hypertension.

关 键 词：lncRNA MRAK048635P1 MIRNAS 靶基因 VSMC 生物信息学 

分 类 号：R318.04[医药卫生—生物医学工程]