由于胰腺癌发展隐匿迅速且易于转移，其预后极差。MEX3A在肿瘤的发生、发展过程中发挥重要作用，但其分子机制尚不明确。本课题组在前期研究中首次发现MEX3A在胰腺癌组织中表达上调且与患者预后负相关，其功能丧失能够抑制胰腺癌侵袭、进展以及上皮-间质转化（EMT）。为进一步研究MEX3A调控胰腺癌的下游分子机制，本项目预实验采用蛋白质组学分析发现VAMP8是MEX3A潜在的下游靶标，MEX3A可能通过结合作用调控VAMP8的蛋白表达，而VAMP8敲减能够抑制胰腺癌细胞增殖并促进凋亡，进一步综合蛋白质组学以及转录组学的下游信号通路富集分析结果，我们推测：MEX3A可能通过结合VAMP8调控其表达水平，进而通过激活STAT3信号通路最终促进胰腺癌进展转移。本课题组将运用基因干预、原位移植瘤模型及活体成像、免疫荧光、免疫共沉淀等方法验证项目假说，为胰腺癌的治疗提供一个新的潜在靶点和思路。

Due to its rapid development and prone to metastasis, the prognosis of pancreatic cancer is extremely poor. MEX3A plays an important role in the development of tumors, but its molecular mechanism remains unclear. In our previous study, we found for the first time that the expression of MEX3A was upregulated in pancreatic cancer and negatively correlated with the prognosis of patients. Loss-of-function experiment showed that MEX3A knockdown could inhibit the invasion, progression and epithelial-mesenchymal transformation (EMT) of pancreatic cancer. In order to further study the downstream molecular mechanism of MEX3A regulating pancreatic cancer, the proteomic analysis showed that VAMP8 is a potential downstream target of MEX3A. MEX3A may regulate the protein expression of VAMP8 through binding, and vamp8 knockdown can inhibit the proliferation and promote apoptosis of pancreatic cancer cells. Further integrate the downstream signaling pathway enrichment of proteomics and transcriptomics results, we proposed the hypothesis that MEX3A/VAMP8 axis promotes development and metastasis of pancreatic cancer through regulation of STAT3 signaling pathway. Our team will use the methods of gene intervention, orthotopic transplantation tumor model, In-vivo imaging system, immunofluorescence and Co-Immunoprecipitation toverify the hypothesis of this project, providing a new potential target and idea for the treatment of pancreatic cancer.