文章摘要

小儿扩张型心肌病血清蛋白及microRNA表达谱的生物信息学分析和发病机制

作者: 1刘娜, 2赵倩倩, 3尤红俊
1 陕西省人民医院儿科,西安 710068
2 空军军医大学第一附属医院临床免疫科,西安 710032
3 陕西省人民医院心血管内科,西安 710068
通讯: 尤红俊 Email: 514044120@qq.com
DOI: 10.3978/j.issn.2095-6959.2022.09.003

摘要

目的:对小儿扩张型心肌病(pediatric dilated cardiomyopathy,PDCM)血清蛋白及microRNA(miRNA)表达谱进行生物信息学分析,探讨其发病机制。方法:对PDCM血清蛋白芯片数据进行差异分析及基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。对PDCM miRNA表达谱挑选部分差异表达miRNA,预测靶基因,与差异血清蛋白/基因取交集,获取共享基因,构建miRNA-mRNA关系对,并行GO和KEGG通路富集分析。结果:PDCM差异血清蛋白富集到细胞黏附调节、免疫调控、含胶原的细胞外基质等GO子集中。差异蛋白主要参与趋化因子信号通路、肾素分泌、肾素-血管紧张素系统、细胞因子-细胞因子受体相互作用、扩张型心肌病(dilated cardiomyopathy,DCM)、醛固酮的合成和分泌、病毒蛋白与细胞因子及细胞因子受体的相互作用等10条信号通路中。4个下调miRNA行靶基因预测后与差异血清蛋白/基因取交集,共8个共享基因,即HSPD1LIFRRPS7ANXA2PDPK1EIF4G2AGTPRKCA。共享基因显著富集到心肌肥厚正调控等GO子集中;及醛固酮的合成和分泌及调节钠重吸收、心肌细胞中的肾上腺素能信号和蛋白激酶B-哺乳动物雷帕霉素靶蛋白(Akt-mammalian target of rapamycin,Akt-mTOR)通路等13条通路中。结论:通过分析PDCM血清蛋白及miRNA表达谱,有助于进一步了解该病发病机制,为临床诊疗提供思路。
关键词: 扩张型心肌病;microRNA;差异表达基因;生物信息学;富集分析

Bioinformatics analyses of serum proteins and microRNAs expression profiles and pathogenesis of pediatric dilated cardiomyopathy

Authors: 1LIU Na, 2ZHAO Qianqian, 3YOU Hongjun
1 Department of Pediatrics, Shaanxi Provincial People’s Hospital, Xi’an 710068, China
2 Department of Clinical Immunology, First Affiliated Hospital, Air Force Military Medical University, Xi’an 710032, China
3 Department of Cardiovascular Medicine, Shaanxi Provincial People’s Hospital, Xi’an 710068, China

CorrespondingAuthor: YOU Hongjun Email: 514044120@qq.com

DOI: 10.3978/j.issn.2095-6959.2022.09.003

Abstract

Objective: To implement bioinformatics analyses of the serum proteins and microRNA (miRNA) expression profiles about pediatric dilated cardiomyopathy (PDCM), to explore the pathogenesis. Methods: Differential analyses, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were performed on serum proteins microarray data of PDCM. Partial differentially expressed miRNAs were selected from miRNA expression profile of PDCM, followed by target genes prediction, and shared genes acquisition by overlapping with differential serum proteins/genes to construct miRNA-mRNA matching relation. GO and KEGG pathways enrichment analyses of common genes were also carried out. Results: Differential proteins of PDCM were enriched to multiple GO terms, including regulation of cell adhesion and immune process, collagen-containing extracellular matrix, and etc. Differential proteins were enriched to 10 signal pathways, including chemokine signaling pathway, renin secretion, renin-angiotensin system, cytokine-cytokine receptor interaction, dilated cardiomyopathy, aldosterone synthesis and secretion and viral protein interaction with cytokine and cytokine receptor, etc. predicted target genes of 4 down-regulated miRNAs were overlapped with differential serum proteins/genes, and then 8 common genes were obtained, namely HSPD1, LIFR, RPS7, ANXA2, PDPK1, EIF4G2, AGT, and PRKCA. Eight common genes were enriched to multiple GO terms, including positive regulation of cardiac muscle hypertrophy, etc. and 13 signal pathways, such as aldosterone-regulated sodium reabsorption, aldosterone synthesis and secretion, adrenergic signaling in cardiomyocytes, mTOR signaling pathway, etc. Conclusion: Bioinformatics analyses of the serum proteins and miRNAs expression profiles about PDCM will benefit our further understanding the pathogenesis of the disease and provide clues for clinical diagnosis and treatment.

Keywords: dilated cardiomyopathy; microRNA; differentially expressed genes; bioinformatics; enrichment analysis

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