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先天性巨结肠症中与m6A甲基化相关关键基因的加权基因共表达网络分析及CIBERSORT筛选

Weighted gene co-expression network analysis and CIBERSORT screening of key genes related to m6A methylation in Hirschsprung's disease.

作者信息

Huang Jiaqian, Chen Tingwei, Wang Junjie, Wang Zhiqiang, Huang Shungen

机构信息

Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China.

Department of Biochemistry and Molecular Biology, Medical College, Soochow University, Suzhou, China.

出版信息

Front Genet. 2023 Apr 18;14:1183467. doi: 10.3389/fgene.2023.1183467. eCollection 2023.

Abstract

Hirschsprung's disease (HSCR) is a neural crest disease that results from the failure of enteric neural crest cells (ENCCs) to migrate to the corresponding intestinal segment. The RET gene, which regulates enteric neural crest cell proliferation and migration, is considered one of the main risk factors for HSCR and is commonly used to construct HSCR mouse models. The epigenetic mechanism of m6A modification is involved in HSCR. In this study, we analyzed the GEO database (GSE103070) for differentially expressed genes (DEGs) and focused on m6A-related genes. Comparing the RNA-seq data of Wide Type and RET Null, a total of 326 DEGs were identified, of which 245 genes were associated with m6A. According to the CIBERSORT analysis, the proportion of Memory B-cell in RET Null was significantly higher than that of Wide Type. Venn diagram analysis was used to identify key genes in the selected memory B-cell modules and DEGs associated with m6A. Enrichment analysis showed that seven genes were mainly involved in focal adhesion, HIV infection, actin cytoskeleton organization and regulation of binding. These findings could provide a theoretical basis for molecular mechanism studies of HSCR.

摘要

先天性巨结肠症(HSCR)是一种神经嵴疾病,由肠神经嵴细胞(ENCCs)未能迁移至相应肠段所致。RET基因调控肠神经嵴细胞的增殖和迁移,被认为是HSCR的主要危险因素之一,常用于构建HSCR小鼠模型。m6A修饰的表观遗传机制与HSCR有关。在本研究中,我们分析了基因表达综合数据库(GEO数据库,GSE103070)中的差异表达基因(DEGs),并聚焦于与m6A相关的基因。比较野生型和RET基因敲除型的RNA测序数据,共鉴定出326个DEGs,其中245个基因与m6A相关。根据CIBERSORT分析,RET基因敲除型中记忆B细胞的比例显著高于野生型。采用韦恩图分析来确定所选记忆B细胞模块中的关键基因以及与m6A相关的DEGs。富集分析表明,七个基因主要参与粘着斑、HIV感染、肌动蛋白细胞骨架组织和结合调控。这些发现可为HSCR的分子机制研究提供理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a7/10152065/a4501b138179/fgene-14-1183467-g001.jpg

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