系统挖掘结肠癌生物标志物及其靶向中药抑制剂  

Systematicmining of colon cancer biomarkers and their targeted traditional Chinese medicine inhibitors

作　　者：黄中强[1] 付聪[1] HUANG Zhongqiang;FU Cong(Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430014,China)

机构地区：[1]武汉市中医医院综合药学部,湖北武汉430014

出　　处：《生物技术》2024年第3期327-336,共10页Biotechnology

摘　　要：[目的]基于多重生物信息学和体外实验挖掘结肠癌的生物标志物及其靶向中药抑制剂。[方法]利用多重生物信息学筛选结肠癌及正常样本测序数据中的候选生物标志物。结合实时荧光定量PCR(Quantitative Real-time PCR,qPCR)和人类蛋白质图谱(The Human Protein Atlas, THPA)验证其表达。通过文献和分子对接筛选与其结合较强的中药化合物。[结果]基于度值(degree)获得50个核心基因。其中,烯醇化酶2(Enolase 2,ENO2)和热休克蛋白家族A (Hsp70)成员1A (Heat Shock Protein Family A (Hsp70) Member 1A,HSPA1A)在结肠癌中显著高表达(P<0.05),且主要参与糖酵解和糖异生等通路调控结肠癌的发展进程。穗花杉双黄酮与ENO2和HSPA1A的结合能力较阳性抑制剂相当,是其潜在抑制剂。[结论]ENO2{P=0.00507,Hazard Ratio[95%CI=1.8613(1.10314,1.74171)]}和HSPA1A{P=0.01955,Hazard Ratio[95%CI=1.21316(1.03151,1.4268)]}是结肠癌的候选生物标志物,且穗花杉双黄酮是二者潜在的靶向抑制剂。[Objective]To mine colon cancer biomarkers and their traditional Chinese medicine inhibitors based on multiple bioinformatics and in vitro experiments.[Method]Multiplex bioinformatics was used to screen candidate biomarkers in the sequencing data of colon cancer and normal samples.Their expression was verified by combining real-time fluorescent quantitative PCR(Quantitative Real-time PCR,qPCR)and human protein atlas(The Human Protein Atlas,THPA).The traditional Chinese medicine compounds with strong binding to them were screened by literature and molecular docking.[Result]50 core genes were obtained based on their degrees.Among them,Enolase 2(ENO2)and heat shock protein family A(Hsp70)member 1A(HSPAIA)were significantly highly expressed in colon cancer cell lines(P<0.05),and was mainly involved in the regulation of the development of colon cancer by pathways such as glycolysis and gluconeogenesis.The binding ability of amentoflavone to ENO2 and HSPA1A was equivalent to that of positive inhibitors.[Conclusion]ENO2 and HSPAIA were candidate biomarkers of colon cancer,and amentoflavone was a potential target inhibitor of them.

关 键 词：结肠癌 生物信息学 体外实验 qPCR THPA 生物标志物 分子对接 中药抑制剂 

分 类 号：R737.9[医药卫生—肿瘤]