胶质瘤因其很强的侵袭性和放化疗抵抗而难以治愈。烟酰胺N-甲基转移酶NNMT是一个重要的表观遗传调控酶，参与DNA甲基化、组蛋白修饰及能量代谢。我们前期研究发现，NNMT在胶质瘤细胞中过表达，表达水平与恶性程度正相关，与生存时间负相关；敲减U87、U251细胞的NNMT后，增殖、侵袭、迁移、成球能力显著下降，凋亡增加。进一步通过基因芯片、GEO数据集研究NNMT的下游靶标基因是生长相关蛋白-43 (GAP-43) 。GAP-43具有抑制胶质瘤细胞微管形成、抑制肿瘤细胞间通讯及诱导凋亡的独特作用，但其上游调控方式尚不清楚。我们推测，NNMT表观遗传调控GAP-43表达，通过DNA高甲基化、组蛋白甲基化及去乙酰化等表观遗传重塑，使GAP-43基因沉默，解除其抑癌作用。课题组拟通过临床标本验证、表观遗传学、代谢组学等研究方法阐明NNMT表观遗传调控GAP-43沉默在胶质瘤中的作用。

Glioma is difficult to be cured because of its strong invasiveness and resistance to radiotherapy and chemotherapy. Nicotinamide N-methyltransferase NNMT is an important epigenetic regulatory enzymes, involving in cellular DNA methylation, histone modification and energy metabolism. Our previous study found that NNMT is overexpressed in glioma cells with expression levels positively correlative with malignant degree and negatively correlative with survival time; After knockdown of NNMT in U87 and U251 cells, proliferation, invasion, migration and the tumor ball significantly decreased while apoptosis increased. It is further proved that growth-associated protein-43 (GAP-43) is the downstream target genes of NNMT by gene chip and GEO data set. GAP-43, plays a unique role in inhibiting the formation of canaliculus of glioma cell, inhibiting communication among tumor cells and inducing apoptosis of human glioma cells, even the regulation pattern in upstream is yet to be cleared. We presume that NNMT may epigenetically regulate GAP-43 and cause GAP-43 gene silencing by epigenetic remodeling like DNA hypermethylation, histone methylation and deacetylation, so as to lift its anti-cancer function, The purpose of this study is to clarify the role of NNMT epigenetic regulation on GAP-43 silenced in glioma by the methods including clinical specimen verification, epigenetics and metabolomics。