NK/T细胞淋巴瘤是一种EB病毒相关的恶性肿瘤，其在发生发展过程中的代谢模式如何改变尚不清楚。我们前期代谢组学研究发现：EB病毒阳性淋巴瘤细胞的糖酵解活性显著高于EB病毒阴性淋巴瘤细胞及正常NK细胞；过表达LMP1蛋白的肿瘤细胞的糖酵解增强；此外，差异基因筛选发现LMP1阳性的糖酵解通路关键酶PKM2的表达升高。因此我们推测：EB病毒编码的LMP1蛋白通过糖酵解关键酶PKM2途径促进NK/T细胞淋巴瘤增殖。为验证该假说，本项目拟进一步研究：①LMP1蛋白上调PKM2表达的信号通路机制;②体内、体外实验阐明PKM2在LMP1介导的肿瘤细胞增殖中的作用和分子机制;③检测PKM2在肿瘤组织中的表达并分析其与患者临床病理特征的相关性。本研究有望从代谢角度阐明EB病毒及LMP1在NK/T细胞淋巴瘤发生发展中的作用，发现新的疗效预测和肿瘤治疗的代谢靶点。

As an Epstein-Barr virus (EBV)-associated malignancy, NK/T cell lymphoma (NKTCL) has not yet been elicited on its pathogenesis. During the process of malignant transformation, the metabolic pattern of tumor cells also changed significantly, which supports malignant phenotypes such as immortal proliferation, invasion and metastasis. Currently, no published literature reveals on the metabolic pattern changes of NK/T cell lymphoma cells and the role that EBV and its encoded oncoprotein LMP1 play in the alteration of metabolic pattern. Our preliminary metabolomics analysis showed that glycolysis activity was significantly higher in EBV positive lymphoma cells than EBV negative lymphoma cells and normal NK cells; inhibition of glycolysis reduced cell proliferation, accelerated cell apoptosis, and enhanced drug sensitivity. Overexpression of LMP1 increased the activity of glycolysis, and differential gene expression screening identified that expression of glycolysis-related enzyme PKM2 was upregulated by LMP1. We hypothesize that EBV-encoded LMP1 protein promotes NK / T cell lymphoma proliferation through PKM2, the key glycolytic enzyme. In this application, we propose three specific aims to verify our hypothesis: ①investigate the signaling pathways involved in upregulation of PKM2 expression by LMP1; ②uncover the effects of PKM2 on biological behaviors of tumor cells and the underlying mechanisms via in vitro and in vivo studies; ③examine PKM2 expression in tumor tissues and its correlation with clinical characteristics. Our study aims to elucidate the role of EBV and LMP1 in the development of NK/T cell lymphoma from a metabolic perspective, and explore a novel metabolite therapeutic target in NK/T cell lymphoma.