Mu Fangxiang, Liu Cai, Huo Huyan, Zeng Xianghui, Wang Fang
Department of Reproductive Medicine, Lanzhou University Second Hospital, Lanzhou, China.
Department of Reproductive Medicine, Lanzhou University Second Hospital, Lanzhou, China.
Reprod Biomed Online. 2024 Dec;49(6):104363. doi: 10.1016/j.rbmo.2024.104363. Epub 2024 Jul 8.
As Sjögren's syndrome is an autoimmune disease and an essential factor in recurrent pregnancy loss (RPL), are there gene-related relationships between the pathogenesis of Sjögren's syndrome and RPL?
The gene datasets for Sjögren's syndrome and RPL were obtained from the Gene Expression Omnibus database, and the co-expression modules and shared differentially expressed genes were identified through weighted gene co-expression network analysis (WGCNA) and limma analysis based on sample size. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses were applied to reveal the hidden biological pathways. Additionally, shared hub gene identification, gene set enrichment analysis, association of the hub gene with ferroptosis and immunity, drug sensitivity analysis, single-cell RNA sequencing analysis, and construction of the competing endogenous RNA (ceRNA) network were conducted.
By intersecting the genes from WGCNA and limma analysis, one shared hub gene (KCNN3) was derived, exhibiting up-regulation in Sjögren's syndrome and RPL. There was a positive relationship between KCNN3 and the immune-related gene TLR2. The ceRNA network revealed that XIST was the most shared long non-coding RNA, which may bind competitively with eight microRNA to regulate the expression of KCNN3. Forty-eight drugs were found to be strongly associated with KCNN3 expression, including estramustine and cyclosporine. Moreover, KCNN3 exhibited high expression in RPL endothelial cells of villous tissue.
This is one of the first studies to reveal that Sjögren's syndrome shares common biological pathways with RPL. KCNN3 was identified as the hub gene associated with Sjögren's syndrome and RPL, and may be a new target for mechanistic studies on Sjögren's syndrome and RPL.
由于干燥综合征是一种自身免疫性疾病，且是复发性流产（RPL）的一个重要因素，那么干燥综合征的发病机制与RPL之间是否存在基因相关关系？
从基因表达综合数据库获取干燥综合征和RPL的基因数据集，并通过加权基因共表达网络分析（WGCNA）和基于样本量的limma分析确定共表达模块和共享差异表达基因。应用基因本体论和京都基因与基因组百科全书分析来揭示潜在的生物学途径。此外，还进行了共享枢纽基因鉴定、基因集富集分析、枢纽基因与铁死亡和免疫的关联、药物敏感性分析、单细胞RNA测序分析以及竞争性内源RNA（ceRNA）网络构建。
通过对WGCNA和limma分析的基因进行交叉分析，得出一个共享枢纽基因（KCNN3），其在干燥综合征和RPL中呈上调表达。KCNN3与免疫相关基因TLR2之间存在正相关关系。ceRNA网络显示XIST是最常见的长链非编码RNA，它可能与8种微小RNA竞争性结合以调节KCNN3的表达。发现48种药物与KCNN3表达密切相关，包括雌莫司汀和环孢素。此外，KCNN3在绒毛组织的RPL内皮细胞中高表达。
这是首批揭示干燥综合征与RPL具有共同生物学途径的研究之一。KCNN3被确定为与干燥综合征和RPL相关的枢纽基因，可能是干燥综合征和RPL机制研究的新靶点。
