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中国癌症防治杂志

中国癌症防治杂志 ›› 2020, Vol. 12 ›› Issue (6): 675-680.doi: 10.3969/j.issn.1674-5671.2020.12.14

• 临床研究 • 上一篇    下一篇

m6A结合蛋白IGF2BP1在肝细胞癌中的基因调控网络分析

  

  1. 530021 南宁 广西医科大学附属肿瘤医院；广西医科大学公共卫生学院
  • 出版日期:2020-12-25 发布日期:2021-01-08
  • 通讯作者: 余红平， E-mail: yhp268@163.com
  • 基金资助:
    国家自然科学基金项目（81660567；81460516；81902876）；广西科技计划重点研发项目（桂科AA18221001；桂科AB18050020）；广西自然科学基金项目（2020GXNSFAA259022；2018GXNSFDA050012；2015GXNSFCBl39007）

Gene regulatory network analysis of m6A reader IGF2BP1 in hepatocellular carcinoma

  1. Guangxi Medical University Cancer Hospital; School of Public Health, Guangxi Medical University, Nanning 530021, China
  • Online:2020-12-25 Published:2021-01-08

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摘要： 目的 分析m6A阅读器胰岛素样生长因子2-mRNA结合蛋白1（insulin-like growth factor 2 mRNA-binding protein 1，IGF2BP1）在肝细胞癌（hepatocellular carcinoma，HCC）中的表达水平及其对HCC患者预后的影响，并探讨IGF2BP1在HCC发生发展中的作用及其潜在机制。方法 基于5对HCC癌及相应癌旁组织mRNA-seq数据和TCGA数据库LIHC的mRNA-seq数据综合分析IGF2BP1在HCC中的表达情况，同时利用TCGA数据库中343例HCC患者的临床随访资料分析IGF2BP1表达水平对HCC患者总生存期的影响。基于TCGA数据库筛选IGF2BP1的共表达mRNA，并利用m6Avar在线网站预测mRNA的m6A位点及其RNA结合蛋白等信息，最终构建IGF2BP1的基因调控网络。结果 IGF2BP1基因在HCC中表达上调（log2FC HCC转录组数据=10.684，P<0.001；log2FC TCGA-LIHC数据集=7.032，P<0.001）。生存分析显示IGF2BP1低表达的HCC患者中位生存时间为5.84年，IGF2BP1高表达患者为4.44年，高表达患者总生存期缩短（P=0.011）。22个差异表达的mRNA与IGF2BP1存在靶向结合关系，并与其表达水平呈正相关。其中，HMGA2等15个高表达mRNA的HCC患者总生存期缩短。HMGA2、PEG10、CEP55、RHO、CDC6和KIF23基因中的潜在m6A甲基化位点位于mRNA 3'UTR端的miRNA结合区域。结论 IGF2BP1在HCC中高表达且导致患者总生存期缩短。IGF2BP1可能通过m6A甲基化及miRNA抑制作用的方式上调mRNA的表达，促进HCC发生并导致不良预后。

关键词: 肝细胞癌, m6A, IGF2BP1, 基因调控网络, 预后

Abstract: Objective To analyze the expression level of m6A reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in hepatocellular carcinoma (HCC) and its impact on the prognosis of HCC patients, and explore the role of IGF2BP1 in hepatocellular carcinoma and its underlying mechanism. Methods The mRNA-seq data of 5 pairs of HCC sample and the data from TCGA-LIHC were used to identify the expression of IGF2BP1 in HCC, and the clinical follow-up data of 343 HCC patients in the TCGA database was used to analyze the effect of IGF2BP1 expression on the overall survival of HCC patients. The TCGA database was used to screen the co-expressed mRNA of IGF2BP1, and the m6Avar website was used to predict the m6A locus of mRNA and its RNA binding protein and other information, and finally constructed the gene regulatory network of IGF2BP1. Results IGF2BP1 gene was up-regulated in HCC (log2FC RNA-seq of HCC=10.684, P<0.001;log2FC TCGA-LIHC =7.032, P<0.001). The median survival time of HCC patients with low IGF2BP1 was 5.84 years, while that of patients with high expression was 4.44 years(P=0.011). The 22 differentially expressed mRNAs had a targeted binding relationship with IGF2BP1, and were positively correlated with its expression level. Among them, 15 highly expressed mRNAs such as HMGA2 could shorten the overall survival of HCC patients. In addition, the potential m6A methylation sites of HMGA2, PEG10, CEP55, RHO, CDC6 and KIF23 genes were located in their 3′-UTR miRNA-binding sites. Conclusions IGF2BP1 is highly expressed in HCC and results in shorter overall survival. IGF2BP1 may up-regulate mRNA expression through m6A methylation and miRNA inhibition, thereby promoting the occurrence of HCC and leading to poor prognosis.

Key words: Hepatocellular carcinoma, m6A, IGF2BP1, Gene regulatory network, Prognosis

中图分类号: 

  • R735.7