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The Expression Of MicroRNA In Myotonic Dystrophy Type 1 And Target Genes Prediction

Posted on:2016-12-16Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:2284330464451486Subject:Neurology
Abstract/Summary:PDF Full Text Request
Objectives:To detect the relative qualification of microRNA (miR-146a, miR-182, miR-200c, miR-885) in skeletal muscle from both myotonic dystrophy type 1(DM1) patients and controls based on the previous established microRNA expression profile in DM1. Besides, myo-miRNA(miR-1, miR-133, miR-206)which participates in myogenesis and muscle regeneration and miR-103, miR-107 which had been identified as attractive candidates for binding to the DMPK mRNA were also been included. To analyze the difference of microRNA expression between the two groups and investigate the association between differentially expressed microRNA and clinical characteristics of DM1 patients. Several bioinformatics algorithms were used to predict the potential target genes of differentially expressed microRNA, and their possible association with DM1 pathogenesis was preliminarily investigated.Methods:1. Skeletal muscles were obtained from 12 genetically confirmed DM1 patients and 12 age and sex matched controls. The clinical data of 12 DM1 patients were collected.2. The expression of microRNA (miR-146a, miR-182, miR-200c, miR-885, miR-1, miR-133, miR-206, miR-103 and miR-107) was analyzed using real-time quantitative PCR.3. Statistical analyses were performed with SPSS 20.0 software. Continuous variables were presented as mean and standard deviation (mean ± SD). Statistical significance of differences between distributions was assessed by two-tailed t-test or analysis of variance. All p values were two-sided, and p<0.05 was considered statistically significant.4. Three bioinformatics algorithms (TargetScan, miRanda and PicTar) were used to predict the potential target genes of differentially expressed microRNA, and their possible association with DM1 pathogenesis was preliminarily investigated.Results:1. The relative qualification of miR-146a was lower in skeletal muscle of DM1 patients than controls and had no relevance to clinical parameters of DM1 patients.2. According to three bioinformatics algorithms including TargetScan, miRanda and PicTar, compared with previous selected differentially expressed genes,17 genes were analyzed based on Gene Ontology. Main relevant biologic processes involved neuron differentiation and regulation of cell apoptosis.Conclusions:Lower qualification of miR-146a in muscle tissue of DM1 patient confirmes the dysregulation of microRNA in DM1 again. Through bioinformatics analysis, we propose miR-146a participate in some important biologic process and play a role in the pathogenesis of DM1.
Keywords/Search Tags:Myotonic dystrophy type 1, MiR-146a, Target gene prediction, Bioinformatics
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