远处转移是鼻咽癌治疗失败的最主要原因，我们前期芯片结果发现eIF3c在发生远处转移的鼻咽癌患者中的表达显著升高（Lancet oncol 2018）。预实验结果提示：eIF3c基因可通过影响SNAIL表达促进肿瘤细胞的上皮间质转化，同时影响外泌体分泌促进血管生成。基于前期结果，本项目拟深入探讨eIF3c通过翻译调控SNAIL表达参与鼻咽癌转移的具体机制；其次，探索eIF3c通过调控外泌体影响血管生成的途径及相关机制；最后，明确eIF3c启动子区域甲基化对其表达的调控方式，并通过体内外实验探讨干预甲基化状态对于鼻咽癌细胞迁移侵袭和血管生成的影响。据此，阐明eIF3c促进鼻咽癌远处转移的分子机制，为鼻咽癌个体化治疗提供新的靶点。

Distant metastasis is the main cause of treatment failure and death in nasopharyngeal carcinoma (NPC). In accordance with our previous microarray data, eukaryotic translation initiation factor 3 subunit C (eIF3c) was up-regulated in patients with metastatic NPC compared with those without distant metastasis (Lancet oncol 2018). Our preliminary data showed that eIF3c could induce endothelial-mesenchymal transition(EMT) through SNAIL translation and exosome-induced angiogenesis. Thus, based on our previous data, we will firstly elucidate the molecular mechanism of translational control of SNAIL by eIF3c. Then, we will explore the underlying mechanism of which eIF3c controls the development of exosome-induced angiogenesis. Lastly, we will demonstrate how promoter methylation status could regulate the expression of eIF3c, and will clarify the functional role of aberrant methylation through in vitro and in vivo experiments on migration, invasion and angiogenesis of NPC cell lines. This project will help us elucidate the functional role and molecular mechanism of eIF3c on NPC metastasis, which may provide a potential therapeutic target for patients with NPC.