首页|基于生物信息学分析的miR-125b-1-3p和NR3C1在妊娠糖尿病患者中的表达及临床意义

基于生物信息学分析的miR-125b-1-3p和NR3C1在妊娠糖尿病患者中的表达及临床意义

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目的 通过生物信息学分析探索miR-125b-1-3p和NR3C1在妊娠糖尿病(GDM)患者中的表达及临床意义.方法 在基因表达综合数据库(GEO)中寻找目标数据集并筛选GDM的差异表达miRNA和mRNA,再进行基因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析.利用绘制蛋白-蛋白相互作用(PPI)网络,筛选GDM关键基因,并进行可视化分析.通过GEO数据库和RT-qPCR技术对miR-125b-1-3p和NR3C1的表达量进行验证;利用双萤光素酶报告基因测定miR-125b-1-3p对靶基因NR3C1的直接结合和转录物活性的影响.结果 检索得到样本类型为血浆的GSE186883数据集,共得到267个差异表达miRNA,均为下调miRNA.从GEO数据库中得到1个独立的GDM胎盘脐带血微阵列数据集GSE203346,得到477个差异表达基因,其中下调基因295个,上调基因182个.KEGG分析结果显示,差异表达基因主要与Toll样受体信号通路、自然杀伤细胞介导的细胞毒性、Ⅰ型糖尿病、NOD样受体信号通路相关.从GEO数据库中得到1个独立的妊娠糖尿病胎盘微阵列数据集GSE203346,共有9585个差异表达基因,其中下调基因9245个,上调基因340个.在miRDB中预测到24个miR-125b-1-3p靶基因,在miRTarBase中预测到13个靶基因,在TargetScan中预测到489个靶基因.分析得到与疾病显著相关的miR-125b-1-3p靶基因NR3C1.与正常孕妇相比,GDM患者miR-125b-1-3p的表达水平降低、NR3C1的表达水平升高(P<0.05),NR3C1的水平与miR-125b-1-3p的表达呈负相关(P<0.05).双萤光素酶报告基因检测提示miR-125b-1-3p通过靶NR3C1 mRNA的3'-UTR来抑制NR3C1表达.结论 通过生物信息学分析,miR-125b-1-3p和NR3C1可为GDM寻求潜在分子标志物提供理论依据.
Expression and clinical significance of miR-125b-1-3p and NR3C1 in patients with GDM based on RBM analysis
Objective To explore the potential biomarkers of gestational diabetes mellitus(GDM),analyze the ex-pression and clinical significance of miR-125b-1-3p and NR3C1 in GDM patients,and provide a theoretical basis for the di-agnosis and intervention of GDM.Methods The target dataset was found in Gene Expression Ominbus(GEO)and the differ-entially expressed miRNA and mRNA of GDM were screened.Then,Gene Ontology(GO)and The Kyoto Encyclopedia of Genes and Genomes(KEGG)Database were enriched.We mapped the network of protein-protein interactions(PPI)to screen and visually analyze key GDM genes.The expression levels of miR-125b-1-3p and NR3C1 were verified by GEO database and RT-qPCR.The effect of miR-125b-1-3p on direct binding and transcriptional activity of target gene NR3C1 was deter-mined by dual luciferase reporter gene.Results The GSE186883 dataset of plasma was retrieved,and 267 differentially ex-pressed miRNA were obtained,all of which were down-regulated miRNA.An independent GDM placental cord blood mi-croarray dataset GSE203346 was obtained from GEO database,and 477 differentially expressed genes were obtained,includ-ing 295 down-regulated genes and 182 up-regulated genes.KEGG analysis showed that differentially expressed genes were mainly associated with toll-like receptor signaling pathway,natural killer cell-mediated cytotoxicity,type Ⅰ diabetes,and NOD-like receptor signaling pathway.An independent placental microarray dataset GSE203346 for gestational diabetes mel-litus was obtained from the GEO database,with a total of 9585 differentially expressed genes,including 9245 down-regulated genes and 340 up-regulated genes.24 miR-125b-l-3p target genes were predicted in miRDB,13 in miRTarBase,and 489 in TargetScan.The miR-125b-1-3p target gene NR3C1 was significantly associated with the disease.Compared with normal pregnant women,the expression level of miR-125b-1-3p was decreased and the expression level of NR3C1 was increased in GDM patients(P<0.05),and the level of NR3C1 was negatively correlated with the expression of miR-125b-1-3p(P<0.05).Dual luciferase reporter gene assay suggested that miR-125b-1-3p inhibited NR3C1 expression through 3'-UTR of target NR3C1 mRNA.Conclusion Through bioinformatics analysis,miR-125b-1-3p and NR3C1 can provide a theoretical basis for seeking potential molecular markers in GDM.

miR-125b-1-3pNR3C1gestational diabetesbioinformatics and the analysis

仲晓荣、陆月梅、刘娅、储巧香、张译心、苏敏

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海安市人民医院,江苏南通 226600

南通大学附属医院,江苏南通 226600

miR-125b-1-3p NR3C1 妊娠糖尿病 生物信息学分析

2024

中国优生与遗传杂志
中国优生科学协会

中国优生与遗传杂志

CSTPCD
影响因子:0.527
ISSN:1006-9534
年,卷(期):2024.32(4)