N^6-甲基腺苷参与镉致人肝细胞癌过程的生物信息学分析  

Bioinformatics Analysis about that N^6-methyladenosine Modification Involving in the Process of Cadmium-induced Human Hepatocellular Carcinoma

作　　者：李钰娜 郭艳 黄燕 栗学清 Li Yuna;Guo Yan;Huang Yan(Changzhi Medical College Department of basic medicine)

机构地区：[1]长治医学院基础医学部,046000 [2]长治市人民医院麻醉科

出　　处：《长治医学院学报》2020年第2期114-120,共7页Journal of Changzhi Medical College

基　　金：2019年长治医学院大学生创新创业训练计划项目(2019009)。

摘　　要：目的:探究镉暴露致人肝细胞癌的机制,为进一步研究提供线索。方法:通过基因表达数据库(GEO)下载9份人肝癌细胞HepG2的RNA表达谱数据和氧化应激人源细胞RNA表达谱数据。使用差异基因分析工具GEO2R和生物信息数据库(DAVID)系统分析差异表达基因,并对差异表达基因进行功能注释。通过癌症基因组图谱数据库下载肝细胞患者表达谱数据317份以及正常志愿者数据50份。通过数据挖掘网站,分析肝细胞癌患者m^6A相关分子的表达水平与预后。结果:低剂量镉暴露差异表达基因的生物过程涉及转录调控和血管生成,分子功能涉及转录因子活性、序列特异性DNA结合,细胞组份涉及细胞质的核周区;低剂量镉暴露与氧化应激共同的差异表达基因的生物过程是血管生成;肝细胞癌患者与健康志愿者相比m^6A甲基化酶、m^6A去甲基化酶和m^6A结合蛋白表达均明显升高(P<0.05)。结论:m^6A甲基化酶METTL3、WTAP与m^6A结合蛋白YTHDF1表达水平的高低与肝细胞癌患者预后相关,m^6A修饰可能参与低剂量镉暴露致肝细胞癌的发生发展过程。Objective: To explore the mechanism of human hepatocarcinoma induced by cadmium exposure, and provide clues for further study. Methods: Data of 9 gene expression profiles from human hepatocellular carcinoma cell subjects of cadmium exposure and cell subjects of oxidative stress exposure were obtained from GEO database. The data of differentially expressed genes were analyzed by GEO2 R and functionally annotated by DAVID. Data of 317 gene expression profiles from patient with hepatocellular carcinoma subjects and 50 from normal human were obtained from The Cancer Cenome Atlas. The expression levels of m^6A related genes and the prognosis of patients were analyzed by Ualcan system. Results: The biological process of low-dose cadmium exposure to differentially expressed genes involved transcriptional regulation and angiogenesis;molecular functions involved transcription factor activity, sequence-specific DNA binding, and cell components involved the periplasmic nucleus. The biological process of differentially expressed genes common to low-dose cadmium exposure and oxidative stress was angiogenesis;Compared with healthy volunteers, the levels of m^6A methylases(METTL3, METTL14 and WTAP), m^6A demethylases(FTO and ALKBH5) and m^6A binding protein(YTHDF1) in human hepatocellular carcinoma patients were significantly increased. The expression levels of m^6A methylases(METTL3 and WTAP) and m^6A binding protein YTHDF1 were associated with the prognosis of patients with hepatocellular carcinoma(P<0.05). Conclusion: m^6A modification is possibly involved in the pathological process of hepatocellular carcinoma induced by low dose cadmium exposure.

关 键 词：N^6-甲基腺苷参 镉 肝细胞癌 生物信息学 

分 类 号：R735.7[医药卫生—肿瘤]