前期研究发现，神经酰胺能改变糖酵解水平影响黑色素瘤细胞增殖转移特性。预实验在黑色素瘤中初步证实"神经酰胺→TARDBP和HIF-1α基因→糖酵解→黑色素瘤增殖转移相关生物学行为"调控轴的存在。本课题将首先筛选TARDBP高表达和低表达、HIF-1α高表达和低表达细胞株，构建裸鼠种植瘤和移植瘤模型，从细胞和动物水平验证神经酰胺的改变影响了TARDBP和HIF-1α基因的表达，进一步调控糖酵解水平来影响了黑色素瘤的增殖转移表型；在此基础上，一方面探讨神经酰胺对糖酵解的调控是通过调节糖酵解底物（或产物）浓度变化还是糖酵解关键酶的改变，另一方面探讨何种亚型的神经酰胺对糖酵解水平及增殖转移表型的影响最大；最后在临床上，探讨神经酰胺、TARDBP和HIF-1α基因、糖酵解相关分子在肿瘤标本中的表达情况与患者病情及预后之间的相关性，为黑色素瘤早期诊断治疗和预后监测提供科学依据，形成转化医学研究新模式。

In previous study, we have found that ceramide can influence the proliferation and metastasis characteristic of melanoma cell through the change of glycolysis level. The pilot experiment preliminary confirmed the regulating axis that "ceramide→TARDBP and HIF-1αgene→glycolysis→the proliferation and metastasis related biological behaviour of melanoma cell". In the formal project, we are going to screen the cell lines in which TARDBP is high-expression(or low-expression) and HIF-1αis high-expression(or low-expression).With these cell lines, we will construct the implantation tumor and metastatic tumor model of nude mouse. Then verify the suppose that the change of ceramide can alter the expression of TARDBP and HIF-1αgene resulting the change of melanoma's proliferation and metastasis phenotype through the regulation of glycolysis level. On these basics, on the one hand , we will discuss the question whether ceramide regulate glycolysis through the modulation of glycolysis substrate(product) concentration or the modulation of key enzyme of glycolysis. On the other hand, we will discuss which subtype of ceramide can mostly affect the glycolysis level and proliferation and metastasis phenotype of melanoma. At last, we will discuss the relationship between ceramide、TARDBP and HIF-1αgene、the expression of related molecules in glycolysis and the prognosis and condition of patient. Through these, we can provide science evidence for melanoma early diagnosis，therapy and early warning for prognosis, and construct a new model of study about translational medicine.