2型糖尿病关键信使RNA和微小RNA的鉴定

Identification of key message RNA and microRNA in type 2 diabetes mellitus

目的通过生物信息学方法鉴定2型糖尿病(T2DM)中的关键信使RNA(mRNA)与微小RNA(miRNA)。方法在GEO数据库下载T2DM相关数据集miRNA-Seq和mRNA-Seq。利用在线分析工具GEO2R分析并筛选T2DM和正常组织样品之间差异表达的mRNA和miRNA。针对差异表达的mRNA进行基因本体论和通路富集分析,并构建蛋白质互相作用(PPI)网络。利用在线工具miRDB预测差异表达miRNA的靶基因,取差异表达miRNA的靶基因与差异表达mRNA的交集,绘制miRNA-mRNA网络图,并预测与差异表达miRNA相互作用的转录因子。结果(1)共筛选出40个差异表达的mRNA,主要与成人运动行为、pH调节等生物过程相关,涉及促胰酶素受体信号通路、钙黏着蛋白信号通路、果糖半乳糖代谢信号通路、γ-氨基丁酸合成信号通路、糖酵解等信号通路。通过构建PPI网络共鉴定出3个核心基因,包括表达下调的分泌素受体(SCTR),以及表达上调的促甲状腺激素受体(TSHR)、降钙素相关多肽α(CALCA)。(2)共鉴定出67个差异miRNA,包括66个下调的miRNA和1个上调的miRNA。miRNA-mRNA网络分析结果显示,miRNA-16-5p是下调最明显的miRNA之一,其与miRNA-103a-3p、miRNA-107、miRNA-15b-5p共同靶向调控丙酮酸脱氢酶激酶4(PDK4)。转录因子SP1、早期生长应答因子是差异表达miRNA最显著的潜在靶标。结论SCTR、TSHR、CALCA可能是T2DM病理生理过程的主要参与者。miRNA-16-5p、miRNA-103a-3p、miRNA-107和miRNA-15b-5p通过靶向调控PDK4在T2DM病理生理中起到重要作用。

Objective To identify the key message RNA(mRNA)and microRNA(miRNA)in type 2 diabetes mellitus(T2DM)by bioinformatics.Methods T2DM related datasets(miRNA-Seq and mRNA-Seq)were downloaded from the GEO database.The differentially-expressed mRNAs and miRNAs between T2DM and normal samples were analyzed and screened by using online analyzer GEO2R.For the differentially-expressed mRNAs,Gene Ontology analysis and pathway enrichment analysis were performed,and the protein-protein interaction(PPI)network was established.The targeted genes of differentially-expressed miRNAs were predicted by online analyzer miRDB,and the intersection was conducted between the targeted genes of differentially-expressed miRNAs and differentially-expressed mRNAs,then a miRNA-mRNA network chart was developed,besides,transcription factors interacted with differentially-expressed miRNAs were predicted.Results(1)A total of 40 differentially-expressed mRNAs were identified,and primarily related to biological processes such as adult motor behavior and pH regulation,involving pancreozymin receptor signaling pathway,cadherin signaling pathway,fructose galactose metabolism signaling pathway,gamma-aminobutyric acid synthesis signaling pathway and glycolysis signaling pathway,etc.Three core genes were identified through the PPI network established,including down-regulated secretin receptor(SCTR),up-regulated thyroid-stimulating hormone receptor(TSHR)and calcitonin-related polypeptide alpha(CALCA).(2)Totally 67 differentially-expressed miRNAs were identified,consisting of 66 down-regulated miRNAs and one up-regulated miRNA.miRNA-mRNA network analysis results showed that miRNA-16-5p was one of the most prominently down-regulated miRNAs,targetedly co-regulating pyruvate dehydrogenase kinase 4(PDK4)with miRNA-103a-3p,miRNA-107 and miRNA-15b-5p.Transcription factor SP1 and early growth response factor were the most notable potential targets of differentially-expressed miRNA.Conclusion SCTR,TSHR,and CALCA may be the main participants in the pathophysiological process of T2DM.Moreover,miRNA-16-5p,miRNA-103a-3p,miRNA-107 and miRNA-15b-5p play an important role in the pathophysiology of T2DM through targeted regulation of PDK4.