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Study On The Pathogenesis Of Coronary Atherosclerosis Based On The Network Correlation Of CircRNA-miRNA

Posted on:2019-06-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y W ZhuFull Text:PDF
GTID:2394330545489527Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
BackgroundThe prevalence and mortality of cardiovascular disease?CVD?in China are on the rise.The death of cardiovascular disease accounts for the top cause of death among urban and rural residents.It is estimated that the number of patients with coronary heart disease in China is about 11 million,and coronary heart disease brings a serious burden on society and families [[]].Coronary heart disease is caused by coronary artery atherosclerotic lesions caused by stenosis or obstruction,resulting in myocardial ischemia,hypoxia or necrosis caused by heart disease.With the development of bioinformatics technology,the important role of non-coding RNA in human diseases has gradually been concerned,but there is less research on the relationship between circRNA-mi RNA and coronary heart disease.This study investigated the role of circRNA-mi RNAs in the pathogenesis of coronary atherosclerosis,providing reference data for potential diagnostic markers and treatments for coronary heart disease.ObjectiveAnalyze the gene expression profiles of circRNA and miRNA in peripheral blood of patients with coronary heart disease,screen circRNA and miRNA differentially expressed genes,and construct a circRNA-miRNA interaction network map using bioinformatics methods to find the circRNA-miRNA relationship related to the determination of coronary atherosclerosis.Right,the differential mRNA and mRNA of circRNA and miRNA were analyzed with Disease,GO,and Pathway enrichment to analyze the mechanisms involved in the development of coronary atherosclerosis.MethodAccording to the relevant standards,hospitalized patients in the Department of Cardiology of the First Affiliated Hospital of Xinxiang Medical College were divided into coronary heart disease group and control group,and 10 cases in each group took peripheral blood samples.The total RNA was extracted,and the purity and concentration of total RNA were detected by ultraviolet absorption method.The integrity of total RNA was detected by denaturing agarose gel electrophoresis.According to the results of the test,5 cases were taken from each group and their peripheral blood circRNA and microRNA expression profiles were detected using the Genebiotech Human CircRNA Array V2.0?4x180K?gene chip and Agilent Human microRNA?Human mi RNA Microarray Release 21.0?gene chip.Screen for differentially expressed circRNAs and miRNAs.MitRanda software was used to predict the circRNAs that miRNAs might bind to,and the differential circRNAs and miRNAs corresponding to linear mRNAs were analyzed by Disease,GO,and Pathway enrichment,and the next step in clinical validation of circRNAs and miRNAs was determined by feature comparison.Resultresearch shows:1.There was no statistically significant difference in age,blood pressure,blood glucose,and lipids between the two groups of baseline data.2.Compared with the control group,circRNA and miRNA were differentially expressed in the peripheral blood of coronary heart disease group,among which 110 were differentially expressed,73 were up-regulated and 37 were down-regulated,while 9 were differentially expressed and were up-regulated.Seven,down two.3.CircRNA-miRNA was co-expressed in the peripheral blood of coronary heart disease group,among which has-circ0030769,hascirc0122274,hascirc0079828,and hascircRNA15486161 were associated with mi R-101-5p.4.Enrichment analysis results4.1 Disease analysis of linear mRNA of circRNA revealed 10 diseases,including Fanconi anemia,germ cell tumor,arterial disease,Alzheimer's disease and aortic valve disease?P<0.05?.Analysis of disease-rich mRNA of miRNAs revealed 13 diseases,including rheumatism,plaque,fatty liver,dyslipidemia,and polycystic kidney disease?P<0.05?.4.2 The analysis of GO concentration of linear mRNA of circRNA mainly includes carboxylic acid metabolism,histone methylation,threonine biosynthesis,histone lysine demethylation,and type II hypersensitivity.The cell components mainly include nuclear,mitochondrial nuclear,GMP reductase complex,nuclear endometrium,DNA-dependent protein kinase-DNA ligase 4 complex and so on.Molecular functions include cadherin binding,DNA polymerase binding,low-density lipoprotein receptor activity,lipoprotein particle receptor activity,and demethylase activity.The GO bioanalysis biological processes of linear mRNAs of mi RNAs include multicellular organism development,RNA polymerase II promoter transcriptional regulation,cellular processes,developmental processes,cell differentiation,and the like.The cell composition mainly includes nucleoplasms,cells,organelle parts,cell parts,protein complexes,and the like.Molecular functions include catalytic activity,protein binding,mRNA binding,transcription factor binding,and NADPH oxidase activity.4.3 KEGA Pathway enrichment analysis of circRNA linear mRNAs revealed 31 pathways,including regulation of Fanconi anemia pathway,mitochondrial fatty acid ?-oxidation,fatty acids,triglycerides and so on.KEGG Pathway enrichment analysis of miRNA linear mRNAs revealed 65 pathways including lipid and lipoprotein metabolism,vascular endothelial growth factor?VEGF?,triglyceride,mTOR signaling,leptin,and the like.ConclusionThe circRNA-mi RNAs were network-related and co-expressed in the development of coronary atherosclerosis.Among them,hascirc0030769,hascirc0122274,hascirc0079828,and hascircRNA15486161 may participate in the occurrence of coronary atherosclerosis through miR-101-5p regulation of multiple signaling pathways.process.
Keywords/Search Tags:Coronary heart disease, circRNA, miRNA
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