摘要
目的 基于基因表达综合数据库(GEO)芯片数据获得绝经后骨质疏松症的差异表达基因,探讨其潜在作用靶点与机制。方法 从GEO数据库筛选绝经后骨质疏松症的芯片数据经GEO2R软件处理获取差异基因,利用Uni Prot数据库进行规范、验证,借助STRING数据库获取蛋白质-蛋白质相互作用(PPI)网络,借助Cytoscape3.9.1构建PPI网络并进行拓扑分析,筛选核心基因。采用cluster Profiler、pathview等R包分析差异基因参与的基因本体(GO)功能及京都基因和基因组数据库(KEGG)信号通路,使用微生信平台进行结果可视化。结果 获得差异基因656个,其中下调基因421个,上调基因235个。得到10个核心基因,即VEGFA、KRAS、EP300、IL-2、IL-4、KIT、FOS、CCND1、HGF、CYCS。GO中分子功能、生物过程、细胞成分富集结果各771、4 648、499个,分子功能主要富集在脂肽结合、磷脂结合等,生物过程主要富集在肽酶活性调节、蛋白水解作用负性调节等,细胞成分主要富集在内质囊泡、等离子膜外侧等;KEGG通路富集结果 299条,主要涉及PI3K-Akt信号通路、病毒蛋白与细胞因子和细胞因子受体相互作用、B细胞受体信号通路、造血细胞谱系、Ras信号通路等。结论 筛选所得差异基因和相关信号通路有助于进一步了解绝经后骨质疏松症的靶点与机制,为新药研发提供了新思路。
Objective To obtain the differentially expressed genes of postmenopausal osteoporosis based on Gene Expression Omnibus(GEO)microarray data,and to explore their potential targets and mechanisms.Methods The microarray data of postmenopausal osteoporosis were screened from GEO database,processed by GEO2R software to obtain differential genes,and standardized and verified by UniProt database.The proteinprotein interaction(PPI)network was obtained by using STRING database.The PPI network was constructed by using Cytoscape 3.9.1 and topological analysis was performed to screen core genes.The R packages such as clusterProfiler and pathview were used to analyze the gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway involved in differential genes,and Weishengxin Platform was used to visualize the results.Results A total of 656 differential genes were obtained,including 421 down-regulated genes and 235 up-regulated genes.Ten core genes were obtained,namely VEGFA,KRAS,EP300,IL-2,IL-4,KIT,FOS,CCND1,HGF,and CYCS.The results of molecular function,biological process,and cell component enrichment in GO were 771,4648,and 499,respectively.The molecular functions were mainly concentrated in lipid binding,phospholipid binding,and so on,the biological processes were mainly concentrated in the regulation of peptidase activity,the negative regulation of proteolysis,and so on,and the cellular components were mainly concentrated in the endocytic vesicles,the external side of the plasma membrane,and so on.There were 299 KEGG pathway enrichment results,mainly involving PI3K-Akt signaling pathway,viral protein interaction with cytokines and cytokine receptors,B cell receptor signaling pathway,hematopoietic cell lineage,Ras signaling pathway,etc.Conclusion The selected differential genes and related signaling pathways are helpful to further understand the target and mechanism of postmenopausal osteoporosis,and provide new ideas for the development of new drugs.
作者
穆胜凯
崔晏君
郝连升
王腾腾
刘君
MU Shengkai;CUI Yanjun;HAO Liansheng;WANG Tengteng;LIU Jun(Department of Orthopaedics,Liaocheng Hospital of Traditional Chinese Medicine,Shandong Province,Liaocheng252000,China;Department of Acupuncture and Moxibustion,Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai200030,China;Geriatric Center,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Shandong Province,Jinan250000,China)
出处
《中国医药导报》
CAS
2024年第8期1-6,12,共7页
China Medical Herald
基金
国家自然科学基金青年科学基金资助项目(82205144)
山东省聊城市重点研发计划政策引导类项目(2022YDSF62)。
