近年来科学家们发现RNA腺嘌呤上第6位的甲基化修饰（m6A）在真核生物中广泛存在，但其调控的分子机制及生物学意义目前仍不清楚。关于m6A修饰与肿瘤之间的关联，迄今仍未见任何报道。cMyc是一个重要的转录因子，调控约15%人类基因的表达，并与30-50%人类恶性肿瘤相关。前期研究中，我们报道了cMyc 在调控非编码RNA功能及细胞代谢中的重要作用 （Nature 2009; EMBO J 2015); 在尚未发表的初步结果中，我们发现cMyc在肿瘤细胞中调节m6A修饰相关的重要分子的表达，并因此影响m6A修饰水平以及细胞代谢功能。因此，本项目将以肿瘤细胞为研究体系，系统研究cMyc对m6A修饰的调控作用及其分子机制，并探讨它们对肿瘤代谢重编程以及肿瘤发生发展的影响。本项目的研究目标是在解析m6A修饰形成的分子机制及其与肿瘤之间的关联的同时，揭示cMyc调控转录后修饰并促进肿瘤发病的新机制。

N6-methyladenosine (m6A) has been recently uncovered as a conserved epitranscriptomic modification of mRNAs in eukaryotic cells, however, its underlying regulatory mechanisms and biological functions remain largely elusive. The connection between mRNA m6A modification and cancer development has never been documented. cMyc is an important onco-protein that plays key roles in normal development and carcinogenesis. We and others have reported previously that cMyc is important in facilitating metabolic reprogramming in cancer cells (Gao et al, Nature 2009). Moreover, our unpublished preliminary results indicate that cMyc levels in cancer cells may determine the expression of several factors involved in mRNA m6A modification, with an impact on cellular metabolism. In the study proposed here, we will further investigate how cMyc facilitates mRNA m6A modification and, in particular, we will focus on mRNA m6A modification in metabolic genes and their effects on cancer metabolic reprogramming. The goal for this study is to decipher the link between mRNA m6A modification and cancer development and to identify new mechanisms for the deregulated cMyc in epitranscriptomic modification.