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糖尿病与心肌梗死关联的转录组学分析

Transcriptomic Analysis of the Association Between Diabetes Mellitus and Myocardial Infarction.

作者信息

Song Lijuan, You Wenjun, Wang Peng, Li Feng, Liu Huakun

机构信息

Department of Endocrine, Jining No.1 People's Hospital, Jining, China.

Department of Neurology, Jining No.1 People's Hospital, Jining, China.

出版信息

Exp Clin Endocrinol Diabetes. 2019 Oct;127(9):603-614. doi: 10.1055/a-0619-4412. Epub 2018 Jun 11.

Abstract

BACKGROUND

Diabetes mellitus (DM) is a major risk factor for coronary artery disease (CAD), and the complications of CAD are the leading cause of deaths among people with DM. Herein, this study aims to identify the common genes and pathways between diabetes and myocardial infarction (MI) to provide more clues for the related mechanism studies.

METHODS

Differentially expressed genes (DEGs) were identified using the cutoff (|log2(fold change)|>0.45 and P value<0.05) by the analysis of online datasets (GSE9006 and GSE48060) related to DM and MI respectively. Moreover, the overlapped DEGs between DM and MI were identified, followed by enriched Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. And the independent patient RNA samples were collected for qRT-PCR validation of the mRNA expression of these overlapped genes.

RESULTS

PI3, ACSL1, MMD and MMP were altered in both T1DM and MI, and they were highly related to "regulation of cellular protein metabolic process". Meanwhile, six genes were identified in both T2DM and MI, which are ADM, NFIL3, PI3, SLPI, ACSL1 and MMP9 and significantly related to "negative regulation of endopeptidase activity". And the expression of these genes were validated.

CONCLUSIONS

In summary, we identified the common DEGs and pathways between T1DM or T2DM and MI, and further validated the changes of those DEGs, providing some clues for mechanism study and potentially therapeutic targets.

摘要

背景

糖尿病(DM)是冠状动脉疾病(CAD)的主要危险因素,CAD并发症是DM患者死亡的主要原因。在此,本研究旨在确定糖尿病与心肌梗死(MI)之间的共同基因和通路,为相关机制研究提供更多线索。

方法

通过分别分析与DM和MI相关的在线数据集(GSE9006和GSE48060),使用截断值(|log2(倍数变化)|>0.45且P值<0.05)来鉴定差异表达基因(DEG)。此外,鉴定DM和MI之间重叠的DEG,随后进行基因本体(GO)富集和京都基因与基因组百科全书(KEGG)通路分析。收集独立患者的RNA样本,对这些重叠基因的mRNA表达进行qRT-PCR验证。

结果

PI3、ACSL1、MMD和MMP在1型糖尿病和MI中均发生改变,且它们与“细胞蛋白质代谢过程的调节”高度相关。同时,在2型糖尿病和MI中均鉴定出六个基因,即ADM、NFIL3、PI3、SLPI、ACSL1和MMP9,且它们与“内肽酶活性的负调节”显著相关。并且验证了这些基因的表达。

结论

总之,我们鉴定出了1型糖尿病或2型糖尿病与MI之间的共同DEG和通路,并进一步验证了这些DEG的变化,为机制研究和潜在治疗靶点提供了一些线索。

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