上皮-间质细胞转换（EMT）在胚胎发育、神经管分化发育、癌症浸润和转移等生理和病理过程中起重要的作用。PRMT7是精氨酸甲基转移酶家族II成员，是重要的表观修饰酶。近年来甲基转移酶的自翻译后修饰影响其功能的研究受到广泛关注。但这种修饰如何在癌症的发生发展及侵袭转移过程中发挥作用目前还没有报道。我们的前期工作发现PRMT7能诱导乳腺癌细胞发生EMT并促进乳腺癌的转移，在此过程中PRMT7受到自甲基化修饰，且这一修饰对于其诱导乳腺癌细胞的侵袭转移至关重要。本项目拟在以上工作基础上，在细胞和分子水平上阐明PRMT7的自甲基化在其所诱导MCF10A细胞发生EMT中的作用机制。同时在整体动物水平上确定PRMT7自甲基化修饰在乳腺癌浸润转移中的作用。本研究对深入阐明精氨酸甲基转移酶的自身翻译后修饰与其功能的关系具有重要参考价值。同时也为探索利用PRMT7作为乳腺癌治疗的靶标提供理论和实验基础。

Epithelial-Mesenchymal Transition (EMT) plays a pivotal role in embryogenesis, neuron differentiation and cancer invasion and metastasis. The protein arginine methyltransferase-7 (PRMT7) belonging to Class II PRMTs, is an important epigenetic modifier involved in various biological events. The effects of self-modifications of the protein methyltransferases have attracted enormous research interest in recent years; however, how these modifications influence the function of methyltransferases in cancer development and metastasis have not been reported to date. In earlier studies, we identified that PRMT7 can induce EMT and promote migration and metastasis in human breast cancer cells, and the self-methylation of PRMT7 is essential to its function. In this study, we intend to elucidate the molecular mechanisms of PRMT7 self-methylation that modulates its function in inducing EMT in MCF10A breast epithelial cells, as well as in controlling breast cancer invasion and metastasis, at both cellular and animal levels. This study will provide further insights into the mechanisms of the effects of self-methylation of protein methyltransferases on their functions. Perspectively, data arising from this study may also be valuable in the exploration of PRMT7 as a therapeutic target for breast cancer.