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  

Expression and clinical significance of miR-125b-1-3p and NR3C1 in patients with GDM based on RBM analysis

作　　者：仲晓荣 陆月梅 刘娅 储巧香 张译心 苏敏[2] ZHONG Xiaorong;LU Yuemei;LIU Ya;CHU Qiaoxiang;ZHANG Yixin;SU Min(Haian People's Hospital,Nantong,Jiangsu 226600,China;Afiliated Hospital of Nantong University,Nantong,Jiangsu 226600,China)

机构地区：[1]海安市人民医院,江苏南通226600 [2]南通大学附属医院,江苏南通226600

出　　处：《中国优生与遗传杂志》2024年第4期706-714,共9页Chinese Journal of Birth Health & Heredity

摘　　要：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。Objective To explore the potential biomarkers of gestational diabetes mellitus(GDM),analyze the expression and clinical significance of miR-125b-1-3p and NR3C1 in GDM patients,and provide a theoretical basis for the diagnosis and intervention of GDM.Methods The target dataset was found in Gene Expression Ominbus(GEO)and the differentially 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 determined by dual luciferase reporter gene.Results The GSE186883 dataset of plasma was retrieved,and 267 differentially expressed miRNA were obtained,all of which were down-regulated miRNA.An independent GDM placental cord blood microarray dataset GSE203346 was obtained from GEO database,and 477 differentially expressed genes were obtained,including 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 mellitus 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-1-3p 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

关 键 词：miR-125b-1-3p NR3C1 妊娠糖尿病 生物信息学分析 

分 类 号：R714.256[医药卫生—妇产科学] Q811.4[医药卫生—临床医学]