2型糖尿病microRNA表达谱及其信号通路研究

发布时间：2018-02-27 13:18

本文关键词： 2型糖尿病动物模型 microRNA　出处：《华南理工大学》2015年硕士论文　论文类型：学位论文

【摘要】：2型糖尿病(Type 2 diabetes,T2D)是一种世界性广泛流行的代谢性紊乱疾病,常伴随有胰岛素分泌不足,胰岛素抵抗,高血糖症以及脂代谢紊乱等症状。T2D患者的数目每年呈现上升的趋势。microRNA(miRNA)是一种短片段的RNA,能够特异性结合到目标基因的3’UTR区域,使目标基因表达受到抑制。目前的研究逐渐表明,miRNA与多种疾病的产生具有相关性。通过对miRNA在T2D病理过程中的具体调控机制的探究,有助于为日后的对T2D的医疗诊断和治疗打下基础。本研究主要使用高通量测序、比较基因组学、生物信息学的方法,尝试阐述miRNA在T2D中的作用及调控机制。首先,采用食蟹猴作为动物模型,利用高通量测序对普通喂食的T2D猴和高脂高糖喂食诱导的T2D猴进行全血miRNA的表达谱分析。通过统计分析,筛选出24个差异表达的miRNA。再经过进一步的筛选,发现miR-182在人、大鼠、小鼠和食蟹猴外周血、肌肉、脂肪、肝脏和胰腺中均具有稳定下调的表达趋势。通过对miR-182及已验证靶基因的信号通路分析,推测miR-182的下调表达是导致胰岛素释放不足和胰岛素抵抗的原因之一。另外论文下载了目前为止已发表的T2D的27组miRNA表达谱和95组基因表达谱数据,利用miRNA靶基因数据库,对两种类型的表达谱数据进行整合分析,建立miRNA-靶基因配对谱,最后进行功能聚类分析。结果显示miRNA的差异表达具有物种以及组织差异性的。通过功能聚类分析结果表明miR-150,miR-15b以及miR-34a,这些miRNA与胰岛素的释放不足,胰岛素抵抗以及细胞损伤有关,推测这3个miRNA可能对T2D致病进程具有重要作用。本论文的研究对T2D的诊断治疗有重要的意义,也为疾病机制研究提供了新思路。
[Abstract]:Type 2 diabetes mellitus type 2 diabetes mellitus (T2D) is a worldwide and prevalent metabolic disorder with insulin deficiency and insulin resistance. The number of patients with hyperglycemia and dyslipidemia. T2D patients show an increasing trend each year. MicroRNAs miRNAs are short fragments of RNAs that specifically bind to the 3 UTR region of the target gene. The expression of target gene was inhibited. Recent studies have shown that miRNAs are associated with many diseases. By exploring the specific regulatory mechanism of miRNA in T2D pathology, This study mainly uses high-throughput sequencing, comparative genomics, bioinformatics methods to explain the role and regulatory mechanism of miRNA in T2D. The full-blood miRNA expression profiles of normal and high-fat high-sugar fed T2D monkeys were analyzed by high throughput sequencing. 24 differentially expressed miRNAs were screened. Further screening showed that miR-182 was found in peripheral blood, muscle and fat of human, rat, mouse and crab monkey. There was a tendency of down-regulation in liver and pancreas. The signal pathway of miR-182 and verified target gene were analyzed. It is speculated that the down-regulation of miR-182 is one of the causes of insulin deficiency and insulin resistance. In addition, 27 miRNA expression profiles and 95 gene expression profiles of T2D and 95 gene expression profiles have been downloaded, and the miRNA target gene database has been used. The miRNA-target gene pairing spectrum was established by integrating the data of two types of expression profiles. Finally, functional cluster analysis was carried out. The results showed that the differential expression of miRNA was different in species and tissue. The results of functional cluster analysis showed that miR-150 miR-15b and miR-34a, these miRNA were associated with insufficient insulin release, insulin resistance and cell damage. It is speculated that these three miRNA may play an important role in the pathogenesis of T2D. The study in this paper is of great significance to the diagnosis and treatment of T2D and provides a new idea for the study of the pathogenesis of T2D.
【学位授予单位】：华南理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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