Fan Jiubo, Jiang Hui, Sun Li, Zhang Qin, Liu Haiju
Department of Clinical Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
Department of Clinical Laboratory, Xiangyang Maternal and Child Health Hospital, Xiangyang, China.
Transl Cancer Res. 2021 Sep;10(9):4087-4095. doi: 10.21037/tcr-21-1041.
The aim of this study was to predict the target genes and pathways of (RA) in the treatment of gastric cancer (GC) by an bioinformatics analysis.
The Traditional Chinese Medicine System Pharmacology database was used to obtain the chemical components and target genes of RA. GC-related genes were downloaded from GeneCard website. GO and KEGG enrichment analyses were used to detect the potential mechanisms of RA targets. Hub genes were identified by protein-protein interaction (PPI) network and then verified by quantitative real-time polymerase chain reaction (qRT-PCR) analysis.
Our analyses identified 34 target genes that contribute to the development of GC. GO analysis showed that the biological functions of the target genes mainly included activation of receptors, including the nuclear receptor, steroid hormone receptor, acetylcholine receptor, G-protein coupled serotonin receptor, serotonin receptor and others. According to KEGG analysis, we found that insulin resistance, galactose metabolism, adipocytokine signaling pathway, breast cancer pathway, and cholinergic synapse were the top 5 pathways involving RA target genes. qRT-PCR and immunohistochemical analysis indicated that RA had significant effects on the expression of hub genes, including MYC, CASP3, SP1, MAPK8, PPARG, FOS, and SLC2A1.
Our study revealed the multi-component, multi-target, and multi-mechanisms of RA on GC, which suggest novel therapeutics for GC.
本研究旨在通过生物信息学分析预测雷酸（RA）治疗胃癌（GC）的靶基因和信号通路。
利用中药系统药理学数据库获取RA的化学成分和靶基因。从基因卡网站下载GC相关基因。采用基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析来检测RA靶标的潜在机制。通过蛋白质-蛋白质相互作用（PPI）网络鉴定枢纽基因，然后通过定量实时聚合酶链反应（qRT-PCR）分析进行验证。
我们的分析确定了34个有助于GC发展的靶基因。GO分析表明，靶基因的生物学功能主要包括受体激活，包括核受体、类固醇激素受体、乙酰胆碱受体、G蛋白偶联血清素受体、血清素受体等。根据KEGG分析，我们发现胰岛素抵抗、半乳糖代谢、脂肪细胞因子信号通路、乳腺癌通路和胆碱能突触是涉及RA靶基因的前5条信号通路。qRT-PCR和免疫组织化学分析表明，RA对枢纽基因的表达有显著影响，包括MYC、CASP3、SP1、MAPK8、PPARG、FOS和SLC2A1。
我们的研究揭示了RA对GC的多成分、多靶点和多机制作用，为GC提供了新的治疗方法。
