摘要
目的探索糖尿病(diabetes mellitus,DM)铜死亡(Cuproptosis)生物标志物以及进行药物筛选。方法利用GEO数据库获取糖尿病GSE25724数据集作为训练集并筛选其差异表达基因,从文献获取19个铜死亡相关基因,两者取交集得到糖尿病铜死亡相关基因,对此基因进行验证(GSE23343与GSE20966作为测试集)。对DM铜死亡基因进行基因相关性分析和富集分析。使用DS BIOVIA Discovery Studio 2016软件对关键基因与所预测的化合物进行分子对接。结果共获得6个糖尿病相关的铜死亡基因(DBT、DLD、GLS、PDHB、NFE2L2和LIPT1),他们主要通过调控三羧酸循环的脂化、丙酮酸代谢、糖酵解糖质新生、HIF-1等信号通路而参与有机酸代谢分解、丙酮酸乙酰辅酶A的合成和氨基酸代谢等生物学过程。这6个基因中DLD、DBT、NFE2L2在测试集样本中差异表达显著,且有较好的诊断价值,分子对接显示DLD、DBT可以与叶酸,NFE2L2可与紫铆素,NFE2L2可与木犀草素有较高的结合能力。结论铜死亡相关基因DLD、DBT、NFE2L2在糖尿病的发生发展中起重要作用,本研究为糖尿病的发病机制及治疗研究提供数据支撑。
Objective To explore the biomarkers of cuproptosis in diabetes mellitus(DM)for drug screening.Methods The GEO database was used to obtain GSE25724 dataset of DM as a training set and screen its differentially expressed genes,and 19 cuproptosis-related genes were obtained from the literature.The intersection of the two was used to obtain cuproptosis-related genes in DM,which were then validated(GSE23343 and GSE20966 were used as a test set).Gene correlation and enrichment analyses were performed on cuproptosis-related genes in DM.Molecular docking of key genes with predicted compounds was performed using DS BIOVIA Discovery Studio 2016 software.Results A total of six diabetes-associated cuproptosis-related genes(DBT,DLD,GLS,PDHB,NFE2L2,and LIPT1)were obtained,and they were involved in biological processes such as metabolic catabolism of organic acids,synthesis of pyruvate-acetyl-coenzyme A and amino acid metabolism,mainly through the regulation of the signaling pathways of the tricarboxylic acid(TCA)cycle of lipidation,pyruvate metabolism,glycolytic glucose de novo,and HIF-1.Among these six genes,DLD,DBT and NFE2L2 were significantly differentially expressed in the test set samples and had good diagnostic value.Molecular docking showed that DLD and DBT could have a high binding capacity with folic acid,NFE2L2 with Butin,and NFE2L2 with Luteolin.Conclusion Cuproptosis-related genes DLD,DBT,and NFE2L2 play an important role in the occurrence and development of DM,and this study provides data support for the studies of the pathogenesis and treatment of DM.
作者
张楠楠
田思思
林登梅
李军
ZHANG Nan-nan;TIAN Si-si;LIN Deng-mei;LI Jun(Department of Pharmacology,School of Basic Medical Sciences,Guizhou University of Traditional Chinese Medicine,Guizhou Province,Guiyang 550025,China;Grade 2021,Class of Medical Experimental Technology,School of Basic Medical Sciences,Guizhou University of Traditional Chinese Medicine,Guizhou Province,Guiyang 550025,China;Grade 2020,Class of Chinese Pharmacy,School of Basic Medical Sciences,Guizhou University of Traditional Chinese Medicine,Guizhou Province,Guiyang 550025,China;Department of Medical Laboratory Technology,School of Basic Medical Sciences,Guizhou University of Traditional Chinese Medicine,Guizhou Province,Guiyang 550025,China)
出处
《河北医科大学学报》
CAS
2024年第5期573-579,共7页
Journal of Hebei Medical University
基金
贵州省卫生健康委科学技术基金(gzwkj2023-266)
贵州省科技厅自然科学项目(黔科合基础ZK-[2023]一般428)。
关键词
糖尿病
铜死亡
计算生物学
diabetes mellitus
cuproptosis
computational biology