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Serum MiR-155 And Its Target Gene Hypoxiainducible Factor 1? (HIF1A) Are Associated With Acute Ischemic Stroke

Posted on:2018-10-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:X P WangFull Text:PDF
GTID:1364330542494652Subject:Neurology
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Background Acute ischemic stroke(AIS)is one of the leading causes of death and disability all over the word.Micro RNAs(miRNAs)have been identified as potential biomarker in diagnosis,treatment and prognosis of AIS.It is common in life activities and plays an important role in the development of tumors,metabolic diseases,cerebrovascular disease and infectious diseases.miRNAs is one of the most important components of epigenetic regulatory mechanism and plays a vital role in the occurrence and development of cerebrovascular disease.A large number of studies have demontrated that low oxygen induced factor 1 alpha(hypoxiainage 1 alpha,HIF1A)is closely related to AIS.HIF1 A regulates oxygen metabolism in the cell's environment and regulates the ability of cells or tissues to regulate the physiological disorders of low oxygen by activating the transcription of downstream genes.Studies have shown that HIF1 A can induce the expression and transcription of dozens of downstream genes.It play important roles in biological activities of many types of cells.In this study,the expression levels of miR-23 b,miR-106 b,miR-130 a,miR-155,and miR-425 were detected in serum of AIS patient and healthy control by using reverse transcription quantitative polymerase chain reaction(RT-q PCR)assay.We found that miR-155 was significantly up-regulated in serum of AIS patients compared with healthy control.Using miRBase and Target Scan databases,we identified miR-155 as a possible regulator of the HIF1A(hypoxiainducible factor 1?).Objectives Test and compare the acute ischemic cerebral apoplexy patients and healthy controls group in the peripheral blood circulation miR-23 b,miR-106 b,miR-130 a and miR-155 and miR-425 expression levels of miR-155 and target HIF1 A gene associated with AIS,as well as the feasibility of AIS risk prediction markers.Methods Using case-control study.Selection of 100 AIS patients and 100 healthy people and extract the elbow vein blood,whole blood extract total RNA.Using real-time fluorescent quantitative PCR method,detection of two groups of peripheral blood circulation miR-23 b,miR-106 b,miR-130 a and miR-155,miR-425,and expression of HIF1 A quantity if there is a difference.SPSS21.0 software is used to analyse the data statistical analysis,the use of One Sample K-S inspection method for continuous variables to normality,distribution with mean + /-standard deviation(x + S)and USES the Student 'S t test.Comparison between the two groups or more groups of samples the Mann-Whitney U inspection or multiple independent Sample rank and inspection(H)to compare differences between groups,classification comparison between data set by chi-square test.Logistic regression of miRNAs and HIF1 A correlation analysis with the incidence of acute ischemic stroke,and using ROC curve analysis evaluation of miRNAs in acute ischemic stroke risk prediction value.Results The expression level of miR-155 in case group was significantly higher than that of the healthy control group,and the difference was statistically significant.No significant difference was found in the level of expression of the other four miRNAs;Multifactor Logistic regression analysis,miR-155's OR value of 5.352;The ROC curve analysis of miR-155 combines the traditional risk factors of AIS,and the area under the curve is 0.832.The expression level of HIF1 A was significantly lower than that of the healthy control group,and the difference was statistically significant.The ROC curve was analyzed by HIF1 A combined with miR-155,and the area under the curve was 0.842.Conclusions 1.High-expression miR-155 and low expression HIF1 A all suggest poor prognosis.2.There was a significant correlation between the expression levels of mir-155 and the HIF1 A in foreign weeks.3.Peripheral blood miR-155 and HIF1 A are expected to be the biomarkers for the risk prediction for AIS.High miR-155 combined with low HIF1 A can dramticlly optimize prediction models based on traditional risk factors.
Keywords/Search Tags:AIS, miRNAs, miR-155, HIF1A, serum
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