m6A RNA修饰在肝细胞癌（HCC）发生发展中有重要功能，HCC中m6A甲基化谱有何关键性改变？哪些因子参与到这一进程？尚缺乏深入研究。在前期工作中，我们通过系统生物学发现HCC特异性m6A甲基化谱与MOV10密切相关。进一步预实验发现：MOV10在HCC组织中显著上调，且MOV10对靶RNA结合具有显著m6A偏好；初步分子实验表明MOV10依赖m6A促进靶RNA稳定，细胞实验表明MOV10促进HCC增殖。据此我们提出假设：MOV10依赖m6A调控靶标RNA稳定性，促进HCC发生发展。本项目通过meRIP-seq联合CLIP-seq明确MOV10依赖m6A调控的潜在靶标，再通过miCLIP-seq结合RNA EMSA、蛋白质谱等手段以及肿瘤原位移植小鼠模型，进一步阐明MOV10在HCC发生发展中的作用和分子机理。本项目的深入开展有望揭示新的m6A调控机制，也将有助于发现新的癌症药物靶点。

N6-methyladenosine (m6A) is a methyl modification on RNA with key roles in hepatocellular carcinoma (HCC). However, we now know little concerning the signature of the HCC m6A RNA methylome and the m6A related factors involved in HCC progression. In our previous report, through system biology methods, we found that HCC specific m6A RNA methylome was significantly correlated with MOV10. In the following experiment we found that MOV10 was overexpressed in HCC tissues, and that MOV10 bound to its target RNAs in preference to m6A. We further revealed that MOV10 stabilized its target RNAs in an m6A dependent manner and that MOV10 depletion significantly impaired the propagation of HCC cells. According to these findings, we propose that MOV10 promotes the initiation and progression of HCC through regulation of RNA stability in an m6A dependent manner. In this program, we will use meRIP-seq and CLIP-seq to identify MOV10 candidate targets, and then we will use miCLIP-seq together with RNA EMSA, LC-MS/MS and mouse models with tumor xenograft to elucidate the role and molecular mechanism of MOV10 in HCC. This study will help to draw out a novel mechanism of m6A regulation, and will also pave the way to the identification of new drug targets.