Xiao Yunyue, Shi Min, Xiao Jiahong, Xie Xiaojuan, Song Ning, Li Minmin, Guo Tao, Chen Wensheng
Department of Gastroenterology, the First Affiliated Hospital (Southwest Hospital), Army Medical University (Third Military Medical University), Gaotanyan Zhengjie 30, Shapingba District, Chongqing, 40038, China.
Department of Pathophysiology, School of Basic Medical Sciences, Shandong Second Medical University, Baotong West Street 7166, Weifang, 261053, China.
Dig Dis Sci. 2025 Jan;70(1):245-261. doi: 10.1007/s10620-024-08736-8. Epub 2024 Nov 18.
Emerging evidence indicates a robust association between internal RNA N7-methylguanosine (m7G) modification and hepatocarcinogenesis. However, the precise implications of altered internal m7G modifications within mRNA on the progression of Hepatitis B Virus (HBV)-induced Hepatocellular Carcinoma (HCC) remain inadequately elucidated.
This study utilized a previously published dataset from the Gene Expression Omnibus (GEO) that includes samples of normal liver tissue, HBV positive (HP) liver tissue, and HP HCC tissue to investigate the profiling of mRNA internal m7G methylation. The STRING database and in vitro experiments were employed for the screening and validation of key m7G-related genes. The Cancer Genome Atlas cohorts were utilized to analyze the association of these key genes with the prognosis of HCC patients.
Comparative analyses revealed internal m7G modification alterations in 1546 mRNAs between HP liver and normal liver tissues, and in 3424 mRNAs between HP HCC and HP liver tissues. Following Protein-Protein Interaction (PPI) network analyses, validation experiments confirmed sustained high levels of internal m7G methylation modifications in EZH2, SMARCA4, and YY1. Furthermore, these genes were found to exhibit m7G modification-dependent expression changes during the transition from HBV infection to HCC, and were closely associated with the prognosis of HCC patients.
This study provides validation of substantial dynamic alternations in mRNA internal methylation profiles during the HBV infection to HCC. EZH2, SMARCA4, and YY1 emerge as promising molecular targets within this intricate regulatory landscape, offering avenues for further research and potential therapeutic exploration.
新出现的证据表明，内部RNA N7-甲基鸟苷（m7G）修饰与肝癌发生之间存在密切关联。然而，mRNA内m7G修饰改变对乙型肝炎病毒（HBV）诱导的肝细胞癌（HCC）进展的确切影响仍未得到充分阐明。
本研究利用了先前发表的来自基因表达综合数据库（GEO）的数据集，该数据集包括正常肝组织、HBV阳性（HP）肝组织和HP HCC组织的样本，以研究mRNA内部m7G甲基化谱。使用STRING数据库和体外实验对关键的m7G相关基因进行筛选和验证。利用癌症基因组图谱队列分析这些关键基因与HCC患者预后的关联。
比较分析显示，HP肝组织与正常肝组织之间有1546个mRNA的内部m7G修饰发生改变，HP HCC组织与HP肝组织之间有3424个mRNA的内部m7G修饰发生改变。经过蛋白质-蛋白质相互作用（PPI）网络分析，验证实验证实EZH2、SMARCA4和YY1中内部m7G甲基化修饰持续高水平。此外，发现这些基因在从HBV感染到HCC的转变过程中表现出依赖m7G修饰的表达变化，并且与HCC患者的预后密切相关。
本研究验证了从HBV感染到HCC过程中mRNA内部甲基化谱存在大量动态变化。在这一复杂的调控格局中，EZH2、SMARCA4和YY1成为有前景的分子靶点，为进一步研究和潜在的治疗探索提供了途径。
