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Abstract：
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder with severe comorbidities. A multiomics approach can facilitate the identification of novel therapeutic targets and biomarkers with proper validation of potential microRNA (miRNA) interactions.
OBJECTIVE: The aim of this study was to identify significant differentially expressed common target genes in various tissues and their regulating miRNAs from publicly available Gene Expression Omnibus (GEO) data sets of patients with T2DM using in silico analysis.
METHODS: Using differentially expressed genes (DEGs) identified from 5 publicly available T2DM data sets, we performed functional enrichment, coexpression, and network analyses to identify pathways, protein-protein interactions, and miRNA-mRNA interactions involved in T2DM.
RESULTS: We extracted 2852, 8631, 5501, 3662, and 3753 DEGs from the expression profiles of GEO data sets GSE38642, GSE25724, GSE20966, GSE26887, and GSE23343, respectively. DEG analysis showed that 16 common genes were enriched in insulin secretion, endocrine resistance, and other T2DM-related pathways. Four DEGs, MAML3, EEF1D, NRG1, and CDK5RAP2, were important in the cluster network regulated by commonly targeted miRNAs (hsa-let-7b-5p, hsa-mir-155-5p, hsa-mir-124-3p, hsa-mir-1-3p), which are involved in the advanced glycation end products (AGE)-receptor for advanced glycation end products (RAGE) signaling pathway, culminating in diabetic complications and endocrine resistance.
CONCLUSIONS: This study identified tissue-specific DEGs in T2DM, especially pertaining to the heart, liver, and pancreas. We identified a total of 16 common DEGs and the top four common targeting miRNAs (hsa-let-7b-5p, hsa-miR-124-3p, hsa-miR-1-3p, and has-miR-155-5p). The miRNAs identified are involved in regulating various pathways, including the phosphatidylinositol-3-kinase-protein kinase B, endocrine resistance, and AGE-RAGE signaling pathways.
OBJECTIVE: The aim of this study was to identify significant differentially expressed common target genes in various tissues and their regulating miRNAs from publicly available Gene Expression Omnibus (GEO) data sets of patients with T2DM using in silico analysis.
METHODS: Using differentially expressed genes (DEGs) identified from 5 publicly available T2DM data sets, we performed functional enrichment, coexpression, and network analyses to identify pathways, protein-protein interactions, and miRNA-mRNA interactions involved in T2DM.
RESULTS: We extracted 2852, 8631, 5501, 3662, and 3753 DEGs from the expression profiles of GEO data sets GSE38642, GSE25724, GSE20966, GSE26887, and GSE23343, respectively. DEG analysis showed that 16 common genes were enriched in insulin secretion, endocrine resistance, and other T2DM-related pathways. Four DEGs, MAML3, EEF1D, NRG1, and CDK5RAP2, were important in the cluster network regulated by commonly targeted miRNAs (hsa-let-7b-5p, hsa-mir-155-5p, hsa-mir-124-3p, hsa-mir-1-3p), which are involved in the advanced glycation end products (AGE)-receptor for advanced glycation end products (RAGE) signaling pathway, culminating in diabetic complications and endocrine resistance.
CONCLUSIONS: This study identified tissue-specific DEGs in T2DM, especially pertaining to the heart, liver, and pancreas. We identified a total of 16 common DEGs and the top four common targeting miRNAs (hsa-let-7b-5p, hsa-miR-124-3p, hsa-miR-1-3p, and has-miR-155-5p). The miRNAs identified are involved in regulating various pathways, including the phosphatidylinositol-3-kinase-protein kinase B, endocrine resistance, and AGE-RAGE signaling pathways.
摘要：
背景：2型糖尿病（T2DM）是一种具有严重合并症的代谢紊乱。通过正确验证潜在的microRNA（miRNA）相互作用，多组学方法可以促进新的治疗靶标和生物标志物的鉴定。
目的：本研究的目的是使用计算机模拟分析从公开的T2DM患者的基因表达综合（GEO）数据集中鉴定不同组织中显著差异表达的共同靶基因及其调节miRNA。
方法：使用从5个公开可用的T2DM数据集中鉴定的差异表达基因（DEG），我们进行了功能富集，coexpression,和网络分析以确定路径，蛋白质-蛋白质相互作用，和miRNA-mRNA相互作用参与T2DM。
结果：我们分别从GEO数据集GSE38642、GSE25724、GSE20966、GSE26887和GSE23343的表达谱中提取了2852、8631、5501、3662和3753DEGs。DEG分析显示，16个常见基因在胰岛素分泌中富集，内分泌抵抗，和其他T2DM相关通路。四个DEG,MAML3,EEF1D,NRG1和CDK5RAP2在通常靶向的miRNA调节的簇网络中很重要（hsa-let-7b-5p，hsa-mir-155-5p,hsa-mir-124-3p,hsa-mir-1-3p)，参与晚期糖基化终产物（AGE）-晚期糖基化终产物受体（RAGE）信号通路，最终导致糖尿病并发症和内分泌抵抗。
结论：本研究确定了T2DM患者的组织特异性DEGs，尤其是关于心脏，肝脏,和胰腺。我们确定了总共16个常见的DEG和前四个常见的靶向miRNA（hsa-let-7b-5p，hsa-miR-124-3p,hsa-miR-1-3p,并具有-miR-155-5p）。鉴定的miRNA参与调节各种途径，包括磷脂酰肌醇-3-激酶-蛋白激酶B，内分泌抵抗，和AGE-RAGE信号通路。
目的：本研究的目的是使用计算机模拟分析从公开的T2DM患者的基因表达综合（GEO）数据集中鉴定不同组织中显著差异表达的共同靶基因及其调节miRNA。
方法：使用从5个公开可用的T2DM数据集中鉴定的差异表达基因（DEG），我们进行了功能富集，coexpression,和网络分析以确定路径，蛋白质-蛋白质相互作用，和miRNA-mRNA相互作用参与T2DM。
结果：我们分别从GEO数据集GSE38642、GSE25724、GSE20966、GSE26887和GSE23343的表达谱中提取了2852、8631、5501、3662和3753DEGs。DEG分析显示，16个常见基因在胰岛素分泌中富集，内分泌抵抗，和其他T2DM相关通路。四个DEG,MAML3,EEF1D,NRG1和CDK5RAP2在通常靶向的miRNA调节的簇网络中很重要（hsa-let-7b-5p，hsa-mir-155-5p,hsa-mir-124-3p,hsa-mir-1-3p)，参与晚期糖基化终产物（AGE）-晚期糖基化终产物受体（RAGE）信号通路，最终导致糖尿病并发症和内分泌抵抗。
结论：本研究确定了T2DM患者的组织特异性DEGs，尤其是关于心脏，肝脏,和胰腺。我们确定了总共16个常见的DEG和前四个常见的靶向miRNA（hsa-let-7b-5p，hsa-miR-124-3p,hsa-miR-1-3p,并具有-miR-155-5p）。鉴定的miRNA参与调节各种途径，包括磷脂酰肌醇-3-激酶-蛋白激酶B，内分泌抵抗，和AGE-RAGE信号通路。
