Zhu Jiang, Wang Lingqi, Li Xin, Lan Dexu, Song Lei, Li Yichen, Cheng Yuqi, Zhang Ping
Medical Laboratory Technology College, Daqing Branch of Harbin Medical University, Daqing, Heilongjiang, 163319, China.
Biochem Biophys Rep. 2022 Mar 24;30:101240. doi: 10.1016/j.bbrep.2022.101240. eCollection 2022 Jul.
Alkaline sphingomyelinase (alk-SMase) is phospholipase that creates ceramides and inactivates platelet activating factors during metabolism, and is linked to digestion and cancer prevention. There have been few studies that completely investigate the linked function and identify the genes related to alk-SMase. In this work, RNA sequencing was performed to investigate the function of alk-SMase. Using RNA-seq data, we discovered 95 differentially expressed genes in the liver of wild type (WT) mice and alk-SMase (gene NPP7) knockout (KO) mice. Differentially expressed genes were functionally associated with the inflammatory response, steroid metabolic process and TNF signaling pathway related terms, regulation of carbohydrate biosynthetic process, and Cytochrome P450-arranged by substrate type using Metascape, according to the results of gene ontology functional enrichment analysis. In addition, an integrated PPI and KEGG network was used to investigate the relationship of differentially expressed genes, It was discovered that one module, which contained 21 nodes and 23 interactions, was significantly related to Cytochrome P450 family, which as mediator of phospholipase. To corroborate the RNAseq results, we identified 12 important genes with high expression levels and significant differences in RNAseq for quantitative real-time polymerase chain reaction (qPCR) verification; 7 genes showed difference significantly (P < 0.05). Our research is the first to conduct a comprehensive genome-wide analysis of the alk-SMase knockout model. Alk-SMase is involved in sphingomyelin hydrolysis. In liver tissues lacking alk-SMase expression, the expression levels of seven genes, including Cyp4a14 and Cyp4a10, were altered.
碱性鞘磷脂酶（alk-SMase）是一种磷脂酶，在代谢过程中可生成神经酰胺并使血小板活化因子失活，与消化和癌症预防相关。很少有研究能全面探究其相关功能并鉴定与alk-SMase相关的基因。在这项研究中，我们进行了RNA测序以研究alk-SMase的功能。利用RNA测序数据，我们在野生型（WT）小鼠和alk-SMase（基因NPP7）敲除（KO）小鼠的肝脏中发现了95个差异表达基因。根据基因本体功能富集分析结果，使用Metascape软件，差异表达基因在功能上与炎症反应、类固醇代谢过程、TNF信号通路相关术语、碳水化合物生物合成过程的调控以及细胞色素P450（按底物类型排列）相关。此外，我们使用整合的蛋白质-蛋白质相互作用（PPI）和京都基因与基因组百科全书（KEGG）网络来研究差异表达基因之间的关系，发现一个包含21个节点和23个相互作用的模块与作为磷脂酶介质的细胞色素P450家族显著相关。为了证实RNA测序结果，我们鉴定了12个在RNA测序中具有高表达水平且差异显著的重要基因，用于定量实时聚合酶链反应（qPCR）验证；7个基因显示出显著差异（P < 0.05）。我们的研究首次对alk-SMase敲除模型进行了全面的全基因组分析。alk-SMase参与鞘磷脂水解。在缺乏alk-SMase表达的肝脏组织中，包括Cyp4a14和Cyp4a10在内的7个基因的表达水平发生了改变。
