根皮苷对食管癌细胞系表达谱的影响  

Effect of phlorizin on expression profile of esophageal cancer cell lines

作　　者：杨照环 胡文倩 贾祯贤 谢俞宁 张志 龙月红 邢朝斌 张雪梅 YANG Zhao-huan;HU Wen-qian;JIA Zhen-xian;XIE Yu-ning;ZHANG Zhi;LONG Yue-hong;XING Zhao-bin;ZHANG Xue-mei(Affiliated Tangshan Gongren Hospital,North China University of Science and Technology,Tangshan 063000,China;College of Life Sciences,North China University of Science and Technology,Tangshan 063210,China;School of Public Health,North China University of Science and Technology,Tangshan 063210,China)

机构地区：[1]华北理工大学附属唐山市工人医院,河北唐山063000 [2]华北理工大学公共卫生学院,河北唐山063210 [3]华北理工大学生命科学学院,河北唐山063210

出　　处：《中草药》2021年第23期7236-7243,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81272613)。

摘　　要：目的研究根皮苷对食管癌细胞系表达谱的影响,探索根皮苷作用于食管癌细胞系的信号通路及其潜在功能。方法使用根皮苷处理人食管癌KYSE450细胞,提取总RNA并建立测序文库,进行转录组测序;使用DESeq2程序鉴定差异表达基因,对差异表达基因进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;使用MCODE进行差异基因核心模块筛选,使用GEPIA数据库分析核心模块中的基因对食管癌生存的影响;使用TIMER在线分析根皮苷对食管癌组织免疫细胞浸润的影响。结果转录组测序结果显示,根皮苷处理后的食管癌细胞具有4602个差异表达基因,其中2407个为上调基因,2195个为下调基因。通路富集分析显示,根皮苷对蛋白质加工、胰岛素抵抗、基因复制和细胞周期等信号通路产生影响。在差异表达基因核心模块中,E3泛素蛋白连接酶2(E3 ubiquitin ligase mind bomb 2,MIB2)高表达可降低食管癌患者的总体生存率;环指蛋白19B(ring finger protein19B,RNF19B)、三重基序蛋白69(tripartite motif-containing protein 69,TRIM69)、泛素连接酶(ubiquitin conjugating enzyme,UBC)和克隆E3泛素连接酶(homologous to the E6-associated protein carboxyl terminus domain containing 2,HECTD2)的表达水平可影响食管癌癌组织的纯度以及免疫细胞浸润的类型。结论根皮苷可影响食管癌细胞的转录谱,其差异表达基因主要集中在细胞生长相关的信号通路。Objective To evaluate the effect of phlorizin on expression profile of esophageal cancer cells and further to reveal the signal pathways and potential functions that phlorizin involved in. Methods KYSE450 esophageal cancer cells were treated with phlorizin. Total RNA was extracted and RNA sequencing library was established to perform transcriptome sequencing. Differentially expressed genes were identified using DESeq2 package. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis of differentially expressed genes were performed. Moreover, hub model was evaluated using MCODE and survival analysis was performed using GEPIA. TIMER was used to online analyze effect of phlorizin on immune cell infiltration in esophageal cancer tissue. Results Total 4602 differentially expressed genes were identified of which 2407 were up-regulated and 2195 were down-regulated. Pathway enrichment analysis showed that phlorizin had impact on protein processing, insulin resistance,DNA replication and cell cycle signaling pathways. In the hub module, high expression of E3 ubiquitin ligase mind bomb 2(MIB2)could reduce the overall survival rate of patients with esophageal cancer;Ring finger protein 19 B(RNF19 B), tripartite motif-containing protein 69(TRIM69), ubiquitin conjugating enzyme(UBC) and homologous to the E6-associated protein carboxyl terminus domain containing 2(HECTD2) expression levels could affect the purity of esophageal cancer tissue and type of immune cell infiltration. Conclusion Phlorizin could affect the transcription profile of esophageal cancer cells, of which differentially expressed genes were mainly involved in signal pathways related to cell growth.

关 键 词：根皮苷 食管癌 转录组测序 免疫浸润 E3泛素蛋白连接酶2 环指蛋白19B 三重基序蛋白69 泛素连接酶 克隆E3泛素连接酶 

分 类 号：R285.5[医药卫生—中药学]