肝癌是严重威胁我国人民生命的最主要恶性肿瘤，合理营养膳食是防控肝癌最经济有效的措施。甜菜碱是食物中重要的甲基供体，我们已结题的国自然项目（81273050）发现甜菜碱可降低肝脂变和肝癌的风险，其机制与其影响DNA甲基化有关。近来年mRNA m6A甲基化修饰在细胞癌变过程中调控基因表达从而影响肿瘤的发生发展受到极大关注。我们推测：甜菜碱的供甲基作用是否也通过影响mRNA m6A的甲基化修饰来影响肝癌的发生和发展？未见报导。因此，我们在已建立的“广东肝癌队列”（NCT03297255）中获得的研究对象进行病例对照设计，探索性地研究甜菜碱等甲基供体与mRNA m6A总体甲基化的关联及与肝癌的关系；然后观察甜菜碱干预对裸鼠肝癌实体瘤的影响，并从影响RNA甲基转移酶复合物的核心组分探讨甜菜碱调控mRNA m6A修饰、进而影响癌基因和抑癌基因表达的抑癌新机制。本研究为膳食营养防控肝癌的新靶点提供思路。

Primary liver cancer (PLC) is one of the most malignant tumors that seriously threaten the life of our people, due to its rapid progress and high mortality. Good nutrition status and diet is the most cost-effective measure to prevent and control the progress of PLC. Betaine is an important methyl donor in food. In our previous completed study (supported by the National Natural Science Foundation of China, NO:81273050), we found that betaine can reduce the risk of hepatic fatty lesion and PLC, and the mechanism may be attributed to its effect on DNA methylation. In recent years, methylation of mRNA m6A has caused great concerns because of its potential in the regulation of oncogenes and tumor suppressor genes during cell carcinogenesis. We speculate that the methyl donor role of betaine also affects the occurrence and development of PLC by affecting the methylation of mRNA m6A. However, none of the existing studies have been reported. Thus, in this project, we first design a case-control study to explore the relationship between methyl donors such as betaine and the overall methylation level of mRNA m6A and their relationships with PLC, using the liver cancer tissues/blood samples obtained from the “Guangdong Liver Cancer Cohort” (NCT03297255). Then, we will use the nude mice model to observe the effect of betaine intervention on solid tumors of liver cancer, the methylation of mRNA m6A and related mechanisms will also be evaluated mainly through the core component of mRNA methyltransferase complex (METTL3\METTL14\WTAP). We hope that this study will provide new insights for the dietary/ nutritional prevention of PLC.