针对 EBV LMP-1 基因的 DNA 酶靶向治疗鼻咽癌的方法。

A therapeutic approach to nasopharyngeal carcinomas by DNAzymes targeting EBV LMP-1 gene.

机构信息

Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, China. yanglifang99@hotmail

出版信息

Molecules. 2010 Sep 1;15(9):6127-39. doi: 10.3390/molecules15096127.

Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) has been known to have oncogenic properties during latent infection in nasopharyngeal carcinoma (NPC). Genetic manipulation of LMP1 expression may provide a novel strategy for the treatment of NPC. DNAzymes are synthetic, single-stranded DNA catalysts that can be engineered to bind and cleave the target mRNA of a disease-causing gene. By targeting the LMP1 mRNA, we successfully obtained a phosphorothioate-modified ''10-23'' DNAzyme namely DZ1, through screening a series of DNAzymes. DZ1 could significantly down-regulate the expression of LMP1 in NPC cells, inhibit cell proliferation, metastasis, promote apoptosis and enhance radiosensitivity of NPC through interfering signal pathways which are abnormally activated by LMP1, including NF-κB, AP-1 and STAT3 signal pathways. Together, interfering LMP1 signaling pathway could be a promising strategy to target the malignant phenotypes of NPC.

EB 病毒（EBV）编码的潜伏膜蛋白 1（LMP1）在鼻咽癌（NPC）潜伏感染期间具有致癌特性。LMP1 表达的遗传操作可能为 NPC 的治疗提供一种新策略。脱氧核酶是一种合成的、单链 DNA 催化剂，可以被设计成结合并切割致病基因的靶 mRNA。通过靶向 LMP1mRNA，我们成功地通过筛选一系列脱氧核酶获得了一种硫代修饰的“10-23”脱氧核酶，即 DZ1。DZ1 可以通过干扰 LMP1 异常激活的信号通路，包括 NF-κB、AP-1 和 STAT3 信号通路，显著下调 NPC 细胞中 LMP1 的表达，抑制细胞增殖、转移，促进 NPC 的细胞凋亡，增强 NPC 的放射敏感性。总之，干扰 LMP1 信号通路可能是针对 NPC 恶性表型的一种很有前途的策略。