Identification of key genes involved in type 2 diabetic islet dysfunction: a bioinformatics study
Identification of key genes involved in type 2 diabetic islet dysfunction: a bioinformatics study
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2 型糖尿病胰岛功能障碍关键基因的鉴定：生物信息学研究
DOI：
10.1042/bsr20182172
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发表时间：
2019-05-31
影响因子：
4
通讯作者：
Yang, Liyong
中科院分区：
文献类型：
--
作者：
Zhong, Ming;Wu, Yilong;Yang, Liyong
目的：鉴定胰岛关键差异表达基因（DEGs）并探讨其在2型糖尿病分子过程中的潜在通路。方法：从GEO数据库下载2型糖尿病患者和正常对照的基因表达综合数据库（GSE20966、GSE25724、GSE38642）。通过基于Database for Annotation， Visualization and Integrated Discovery (DAVID) 6.8的富集分析进一步评估deg。然后，利用Search Tool for Retrieval Interacting Genes (STRING) 10.0和基因集富集分析（gene set enrichment analysis， GSEA），我们确定了枢纽基因和相关通路。最后，通过实时荧光定量PCR （qPCR）验证hub基因的表达。结果：三个数据集中共表达了45个deg，其中大部分是下调的。deg主要参与细胞通路、激素应答和结合。在蛋白质-蛋白质相互作用（PPI）网络中，我们发现atp -柠檬酸裂解酶（ACLY）是枢纽基因。GSEA分析提示ACLY低表达富集于甘氨酸、丝氨酸、苏氨酸代谢、药物代谢细胞色素P450 （CYP）和nod样受体（NLR）信号通路。qPCR显示hub基因ACLY的表达趋势与我们的生物信息学分析一致。结论：生物信息学分析显示ACLY及其相关通路可能是2型糖尿病的分子机制靶点。
Aims: To identify the key differentially expressed genes (DEGs) in islet and investigate their potential pathway in the molecular process of type 2 diabetes. Methods: Gene Expression Omnibus (GEO) datasets (GSE20966, GSE25724, GSE38642) of type 2 diabetes patients and normal controls were downloaded from GEO database. DEGs were further assessed by enrichment analysis based on the Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.8. Then, by using Search Tool for the Retrieval Interacting Genes (STRING) 10.0 and gene set enrichment analysis (GSEA), we identified hub gene and associated pathway. At last, we performed quantitative real-time PCR (qPCR) to validate the expression of hub gene. Results: Forty-five DEGs were co-expressed in the three datasets, most of which were down-regulated. DEGs are mostly involved in cell pathway, response to hormone and binding. In protein–protein interaction (PPI) network, we identified ATP-citrate lyase (ACLY) as hub gene. GSEA analysis suggests low expression of ACLY is enriched in glycine serine and threonine metabolism, drug metabolism cytochrome P450 (CYP) and NOD-like receptor (NLR) signaling pathway. qPCR showed the same expression trend of hub gene ACLY as in our bioinformatics analysis. Conclusion: Bioinformatics analysis revealed that ACLY and the pathways involved are possible target in the molecular mechanism of type 2 diabetes.