关键词: 阔叶十大功劳, 肝癌, 铁死亡, AURKA

Abstract: Through network pharmacology and bioinformatics, we explored the mechanism of Mahonia bealei regulating ferroptosis to interfere with liver hepatocellular carcinoma(LIHC). LIHC gene chip data set was downloaded from GEO database, ferroptosis markers were downloaded from FerrDb database, components and targets of M.bealei were obtained from TCMSP, SymMap and SwissTargetPrediction database. Molecular docking was performed using DS BIOVIA Discovery Studio 2016 v16.1 software to search for hub genes; Using Cytoscape software and STRING platform, PPI analysis was performed on the intersection targets of drug-disease-ferroptosis. The GEPIA and TIMER database were used for differential- DOI:10.3969/j.issn.1000-1565.2023.06.006阔叶十大功劳作用于AURKA调控铁死亡干预肝癌的作用李军¹,杨凯平²,林登梅²,朱燚²,张楠楠¹(1.贵州中医药大学 基础医学院,贵州 贵阳 550025;2.贵州中医药大学 药学院,贵州 贵阳 550025)摘 要:探索阔叶十大功劳Mahonia bealei调控铁死亡干预肝癌的机制.从GEO数据库下载肝癌的转录组数据集,从FerrDb数据库下载铁死亡相关基因,使用TCMSP、SymMap、SwissTargetPrediction数据库获取M.bealei的成分与靶点;使用DS BIOVIA Discovery Studio 2016 v16.1软件进行分子对接;运用Cytoscape软件及STRING平台,对药物-疾病-铁死亡交集靶点进行PPI分析;利用GEPIA、TIMER数据库进行差异表达分析;利用UALCAN数据库进行临床相关性分析;利用Kaplan-Meier Plotter数据库进行生存分析;使用THPA数据库进行病理学切片分析;使用Western blot进行体外实验验证;最后,进行转录因子的预测,共筛选出5个M.bealei调控铁死亡干预肝癌的关键基因,通过基因差异表达选取3个核心基因AKR1C3、AKR1C1、AURKA,进一步分析发现AURKA与肝癌生存分析、临床参数、病理学结果均显著相关.Western blot实验证实,与HepG2肝癌细胞组相比,M.bealei含药血清组的AURKA蛋白表达上调(P<0.05).通过以上研究认为M.bealei可通过作用于AURKA调控铁死亡而干预肝癌.关键词:阔叶十大功劳;肝癌;铁死亡;AURKA 中图分类号:R273 文献标志码:A 文章编号:1000-1565(2023)06-0603-13Role of Mahonia bealei in regulating Ferroptosis by AURKA to intervene in Liver hepatocellular carcinoma LI Jun¹, YANG Kaiping², LIN Dengmei², ZHU Yi², ZHANG Nannan¹(1. School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; 2. School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China)Abstract: Through network pharmacology and bioinformatics, we explored the mechanism of Mahonia bealei regulating ferroptosis to interfere with liver hepatocellular carcinoma(LIHC). LIHC gene chip data set was downloaded from GEO database, ferroptosis markers were downloaded from FerrDb database, components and targets of M.bealei were obtained from TCMSP, SymMap and SwissTargetPrediction database. Molecular docking was performed using DS BIOVIA Discovery Studio 2016 v16.1 software to search for hub genes; Using Cytoscape software and STRING platform, PPI analysis was performed on the intersection targets of drug-disease-ferroptosis. The GEPIA and TIMER database were used for differential- 收稿日期:2023-04-19 基金项目:贵州中医药大学学术新苗项目(贵科合学术新苗2023-28);贵州省科技计划项目(黔科合基础ZK［2023］一般428);2023年贵州中医药大学研究生教育创新计划项目(YCXKYB2023001) 第一作者:李军(1986—),男,山东菏泽人,贵州中医药大学副教授,主要从事肝癌及糖尿病药物方面研究.E-mail: lijun763@gzy.edu.cn 通信作者:张楠楠(1989—),女,河南焦作人,贵州中医药大学讲师,博士,主要从事肝癌及糖尿病药物研究.E-mail: doczn@sina.com第6期李军等:阔叶十大功劳作用于AURKA调控铁死亡干预肝癌的作用expression analysis. Clinical correlation analysis was performed using UALCAN data. Kaplan-Meier Plotter database was used for survival analysis. Pathology section analysis was performed using the THPA database. We used Western blot to Verify in vitro experiments Finally, transcription factor prediction and cell experiments were performed. A total of 5 hub genes regulating ferroptosis and interfering LIHC were screened out. Three core genes, AKR1C3, AKR1C1 and AURKA, were selected through gene differential expression. Further analysis found that AURKA was significantly correlated with LIHC survival analysis, clinical parameters and pathological results. We also verified that AURKA protein expression was up-regulated in M.bealei containing serum group compared with HepG2 hepatocellular carcinoma group by Western blot assay(P<0.05). Through the above research, we believe that the M.bealei can intervene in LIHC by acting on AURKA to regulate ferroptosis.

Key words: Mahonia bealei, liver hepatocellular carcinoma, Ferroptosis, AURKA