LMNA基因R527C纯合突变早老症患儿外周血单个核细胞基因表达谱的RNA-Seq分析

RNA-sequencing analysis of gene expression profiling in peripheral blood mononuclear cells of progeria syndrome associated with homozygous R527C LMNA mutation

目的:分析LMNA基因R527C纯合突变早老症患儿外周血单个核细胞基因表达谱的转录组测序(RNA-seq)结果。方法:将3例LMNA基因R527C纯合突变早老症患儿作为病例组,1例正常儿童为对照组,应用RNA-seq技术对两组外周血单个核细胞进行全转录组测序,分析差异表达基因,并对这些差异基因进行GO功能和Pathway显著性富集分析。结果:病例组与对照组差异表达基因共有135个,其中下调91个,上调44个。差异基因功能涉及DNA复制、能量代谢、信号转导、炎症等方面,其中MCM、GINS2、CDC45与DNA复制有关;IL-8、FOS、CXCR2等与炎症有关;TOP2A、ABCG1、KIF4A、KIF2C、KIF20A、KIF14、KIF11、KIF18B、KIFC1、KIF15等与细胞能量代谢有关;BUB1、AURKB、BUB1B、PKMYT1、MELK与蛋白激酶活性有关。GO功能显著性富集分析结果显示:差异基因的功能主要包括生物学行为调控、细胞组分形成及分子功能,集中表现在生物学过程部分行为的调控。Pathway显著性富集分析10条具有显著性差异的通路,其中细胞周期及细胞衰老通路明显富集。结论:调控细胞周期的相关基因的表达量改变可能参与LMNA基因R527C纯合突变早老症患儿疾病的发生和发展。

Objective: To analyze the RNA-sequencing (RNA-Seq) results of gene expression profiling in peripheral blood mononuclear cells (PBMCs) of progeria syndrome associated with homozygous R527C LMNA mutation. Methods: PBMCs were extracted from 3 patients (case group) with progeria syndrome associated with homozygous R527C LMNA mutation and 1 healthy child (control group),respectively.RNA-Sep was used to obtain transcriptome sequences.After the differentially expressed genes (DEGs) of two groups were screened,GO analysis and KEGG signaling pathways analysis were conducted. Results: There were 135 DEGs of the gene expression profiling between the two groups,in which 91 were down-regulated and 44 were up-regulated.The functions of DEGs involved in DNA replication,energy metabolism,signal transduction,inflammation,etc.Among which,MCM,GINS2 and CDC45 were related to DNA replication.IL-8,FOS and CXCR2 were related to inflammation.TOP2A,ABCG1,KIF4A,KIF2C,KIF20A,KIF14,KIF11,KIF18B,KIFC1 and KIF15 were related to ATPase activity.BUB1,AURKB,BUB1B,PKMYT1 and MELK were related to protein serine/threonine kinase activity.The results of GO enrichment analysis showed that the functions of DEGs could be mainly involved in three parts:regulating biological processes,organizing cellular components and performing molecular function.Pathway enrichment analysis showed that the DEGs between the two groups involving in 10 pathways,of which cell cycle and senescence pathways were mostly enriched. Conclusion: Changes in the expression of genes related to the regulation of cell cycle may play an important role in the occurrence and development of progeria syndrome associated with homozygous R527C LMNA mutation.