摘要
目的通过鉴定得出正常和异常O-型糖基化结肠癌细胞之间的差异表达基因(differentially expressed genes,DEGs),即O-型糖基化相关差异基因,并探讨其促进肿瘤发生发展的潜在机制。方法运用单色标记表达谱芯片技术对经Cosmc表达质粒或其空白对照质粒稳定转染的LS174T Tn(+)细胞进行检测,采用RNA杂交获得基因表达谱数据,通过Wegstalt平台的基因通路富集(gene set enrichment analysis, GESA)方法行GO基因本体(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)肿瘤相关通路分析,R语言行热图聚类分析,STRING在线软件对蛋白网络进行差异及整合分析。结果通过分析获得了1 474个符合条件的DEGs,其中有502个基因上调,972个基因下调;GO分析显示DEGs主要参与细胞外基质组织及生长因子活性相关的生物学过程;KEGG分析DEGs主要富集在磷脂酰肌醇-3激酶(phosphatidylinositol 3-kinase,PI3K)、转化生长因子-β(transforming growth factor-β, TGF-β)和Wnt等经典信号通路上。结论本研究首次着眼于结肠癌细胞中由O-型糖基化引起的转录组学变化,有助于揭示O-型糖基化修饰的结直肠癌分子特征,并为科学研究和临床治疗提供新的方向。
Objective To identify differentially expressed genes(DEGs)between normal and abnormal O-glycosylated colon cancer cells,which are regarded as directly O-glycosylation-associated genes,and to investigate their underlying mechanisms.Methods The gene expression profiles of LS174T Tn(+)cells stably transfected with Cosmc or control plasmid were subjected to one-color microarray-based gene expression profiles.After RNA hybridization,gene expression profiles were obtained,and differential and integrative analysis was performed on Wegstalt platform by gene set enrichment analysis(GESA).Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)tumor-related pathways analysis,R software packages,and protein-protein interaction(PPI)networks by STRING were conducted.Results A total of 1474 genes,including 502 up-regulated genes and 972 down-regulated genes,were selected as DEGs.GO analysis demonstrates that both up-regulated and down-regulated DEGs are enriched for numerous biological processes such as extracellular matrix organization and growth factor activity.DEGs are mainly enriched in several tumor-associated pathways such as phosphatidylinositol 3-kinase(PI3K)signaling pathway,transforming growth factor-β(TGF-β)signaling pathway,and Wnt signaling pathway.Conclusion This study is the first work focused on the transcriptional changes caused by O-glycosylation in colon cancer cells,which helps to uncover the molecular characteristics of O-glycosylated colorectal cancer(CRC)cells and may provide new targets for future research and therapy.
作者
姚健楠
高天博
段凌
刘健
蒋玉良
安广宇
葛洋
Yao Jiannan;Gao Tianbo;Duan Ling;Liu Jian;Jiang Yuliang;An Guangyu;Ge Yang(Department of Oncology,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China;Medical Research Center,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China)
出处
《首都医科大学学报》
CAS
北大核心
2020年第3期403-410,共8页
Journal of Capital Medical University
基金
国家自然科学基金(81802738)
北京市自然科学基金(7202051)
北京市属医院科研培育计划(PX2020016)
北京市附属医院科研培养计划(PX2017017)。
