EBV重新激活时BHRF1对鼻咽癌干细胞的诱导作用及其机制研究

Nasopharyngeal carcinoma (NPC) is an endemic malignancy prevalent in South East Asia. Epidemiological studies have associated this disease closely with Epstein-Barr virus (EBV) infection and the virus is commonly under latency type II. The EBV can be reactivated under certain circumstance while it is not clear about the biological and clinical significance of this kind of reactivation. People use cancer stem cells (CSCs) to investigate the correlation between the concurrent chemoradiation resistance and the tumor recurrence and metastasis. The typical clinical manifestation is the significantly increased DNA copies and the elevated antibody titers against various EBV lytic gene products which indicating that the EBV is reactivated in some of the host cells and might became CSCs. The EBV lytic gene BHRF1 is the mimic gene of human bcl-2 and BHRF1 is expressed only in the EBV lytic infection to keep uttermost EBV release but avoid the host cell apoptosis. We firstly set up a theory model that the EBV reactivation enhanced the cancer stem cell formation and then NPC recurrence and metastasis. In this work we intend to investigate the inducion of the cancer stem cells by BHRF1and its expression regulation mechanism when EBV reactivate. Our work will provide molecular biological and cell biological basis for the NPC relapse and metastsis, and provide novel theoretical basis for the clinical interference with the NPC recurrence and metastasis.

鼻咽癌高发于华南地区。EB病毒是NPC重要的致癌生物学因素，且在NPC组织中为II型潜伏感染。在特定条件下EBV在极少数NPC细胞中重新激活为裂解感染，其生物学及临床意义不明。肿瘤干细胞是奠定放化疗抗性导致复发转移的细胞基础，而NPC复发转移的临床特征表现为血清EBV DNA拷贝数和裂解抗体滴度显著升高，提示在部分NPC细胞中EBV已进入裂解周期，这部分细胞可能被诱导为NPC肿瘤干细胞。EBV裂解基因BHRF1基因为人基因bcl-2类似基因，仅在裂解感染时表达，以保证宿主细胞最大限度产生病毒而不凋亡。本项目首次提出BHRF1在EBV重新激活时诱导肿瘤干细胞的产生并促进NPC的复发转移的理论模型。本项目旨在研究EBV重新激活时病毒裂解基因BHRF1诱导NPC肿瘤干细胞产生及其表达调控机制，为NPC的复发转移奠定分子生物学及细胞生物学基础，为临床设计干涉NPC复发转移的策略提供创新性理论依据。

鼻咽癌高发于华南地区。EB病毒是NPC重要的致癌生物学因素，且在NPC组织中为II型潜伏感染。在特定条件下EBV在极少数NPC细胞中重新激活为裂解感染，其生物学及临床意义不明。肿瘤干细胞是奠定放化疗抗性导致复发转移的细胞基础，而NPC复发转移的临床特征表现为血清EBV DNA拷贝数和裂解抗体滴度显著升高，提示在部分NPC细胞中EBV已进入裂解周期，这部分细胞可能被诱导为NPC肿瘤干细胞。EBV裂解基因BHRF1基因为人基因bcl-2类似基因，仅在裂解感染时表达，以保证宿主细胞最大限度产生病毒而不凋亡。本项目首次提出BHRF1在EBV重新激活时诱导肿瘤干细胞的产生并促进NPC的复发转移的理论模型。本项目旨在研究EBV重新激活时病毒裂解基因BHRF1诱导NPC肿瘤干细胞产生及其表达调控机制，为NPC的复发转移奠定分子生物学及细胞生物学基础，为临床设计干涉NPC复发转移的策略提供创新性理论依据。