弥漫性大B细胞淋巴瘤（DLBCL）是具有高度异质性的恶性肿瘤，常见表观遗传学突变及基因的不稳定性，但其恶性转化的分子机制尚未完全阐明。组蛋白甲基转移酶因其酶活性而具有潜在的治疗易感性，本课题组前期研究发现DLBCL中组蛋白甲基转移酶EZH2与NSD2呈现高表达且相关性较高；DLBCL中5个下调的miRNA受EZH2抑制，且预测能结合于NSD2的3’UTR，提示DLBCL中可能存在EZH2-miRNA-NSD2调控轴。为探究EZH2和NSD2在功能上的关系，本项目拟采用基因沉默和高表达等方法，通过体内外实验研究EZH2-NSD2调控轴对DLBCL细胞增殖、成瘤、侵袭的影响，进一步探究EZH2通过miRNA网络对NSD2表达和转录活性的调控，以阐明DLBCL中EZH2-miRNA-NSD2调控轴的作用机制，为DLBCL的分子靶向治疗寻找新靶标提供依据。

Diffuse large B-cell lymphoma (DLBCL) is a group of highly heterogeneous malignant tumors. Mutations in epigenetic related genes and perturbation of epigenomic patterning are frequent events in DLBCL. The molecular mechanism of malignant transformation in DLBCL has not been thoroughly elucidated due to the heterogenity of the tumor. Histone methyltransferases have potential susceptibility to treatment due to their enzyme activities. Our recent work shows that overexpressions of the histone methyltransferases (EZH2 and NSD2) are closely related in DLBCL. Five EZH2-suppressed miRNAs are downregulated in DLBCL and predicted to bind to 3’UTR of NSD2, suggesting that the EZH2-miRNA-NSD2 axis probably play a role in DLBCL. In this study, we propose to explore the function of EZH2-NSD2 axis in cellular proliferation, tumor growth and invasion by gene silencing and overexpression in vitro and in vivo. The miRNA network-mediated regulation of NSD2 by EZH2 will be further investigated. Our study will clarify the mechanism of EZH2-miRNA-NAD2 axis in DLBCL and provide more scientific evidence for molecular targeted therapy of DLBCL.