EBV病毒microRNA BART7 与鼻咽癌细胞的放射敏感性的相互关系及机制

Undifferentiated nasopharyngeal carcinoma (NPC) is highly sensitive to radiation therapy. However, the reason remains unknown. Failure to radiation therapy or the intrinsic radiation resistance is the major obstacle in NPC treatment leading to residue disease and disease recurrence. It is also the major cause of the poor survival rate of NPC patients. Understanding the mechanism behind the radiation sensitivity could allow us to identify molecular target to follow the therapy and predict treatment outcome. Many studies had reported that undifferentiated NPC is closely associated with Epstein-barr virus (EBV). However, there is still no consensus on the key mechanisms induced by the virus in radiation sensitivity. Recently, it was identified that EBV will encoded a small RNA called ebv-miR-BART7 in the NPC cells. Our preliminary data suggested that NPC patients had high ebv-miR-BART7 level in the peripheral blood. NPC patients could be distinguished from the non-cancer individuals based on this plasma ebv-miR-BART7 level. Using transient transfection, we noticed that ebv-miR-BART7 expression in the NPC cell could increase the radiation sensitivity significantly in comparison with the mock control. If the association and correlation between ebv-miR-BART7 and radiation sensitivity is proved experimentally, ebv-miR-BART7 could possibly be used as molecular marker clinically in screening NPC patients and predict the treatment outcome and could improve the prognosis of our NPC patients.

放疗对未分化型鼻咽癌有极佳效果，可是原因不明。恶性肿瘤细胞自身对放射线的抵抗力是鼻咽癌放疗的主要障碍。揭示未分化型鼻咽癌与放疗的关系和机制，有助对抗放疗抵抗机制并为鼻咽癌的放疗敏感度提供可行的分子靶点。未分化鼻咽癌与EBV有密切的关系。研究指出EBV病毒的基因产物会明显改变鼻咽癌细胞对放疗的反应，然而其中关键机制仍没有共识。研究指出EBV病毒会在恶性肿瘤细胞内产生 ebv-miR-BART7。我们已证实鼻咽癌病人的血液样本中ebv-miR-BART7水平比正常人高。以血浆内ebv-miR-BART7水平为分子靶点，可区分鼻咽癌病人和正常个体。利用瞬间转染技术，我们已证明提高ebv-miR-BART7在鼻咽癌细胞株的表达会提升癌细胞对放疗的敏感度。只要证明ebv-miR-BART7与放射敏感性的相互关系，ebv-miR-BART7可作为分子标志物用以筛选及预测放疗成效，提高鼻咽癌的治疗效率。

放疗对未分化型鼻咽癌有极佳效果，可是原因不明。恶性肿瘤细胞自身对放射线的抵抗力是鼻咽癌放疗的主要障碍。揭示未分化型鼻咽癌与放疗的关系和机制，有助对抗放疗抵抗机制并为鼻咽癌的放疗敏感度提供可行的分子靶点。未分化鼻咽癌与EBV有密切的关系。研究指出EBV病毒的基因产物会明显改变鼻咽癌细胞对放疗的反应，然而其中关键机制仍没有共识。研究指出EBV病毒会在恶性肿瘤细胞内产生 ebv-miR-BART7。我们已证实鼻咽癌病人的血液样本中ebv-miR-BART7水平比正常人高。以血浆内ebv-miR-BART7水平为分子靶点，可区分鼻咽癌病人和正常个体。我们证明初发鼻咽癌和复发鼻咽癌组织中的ebv-miR-BART7水平高于正常鼻咽粘膜组织；ebv-miR-BART7过量表达增强鼻咽癌细胞对放疗的敏感度；ebv-miR-BART7通过靶向6-磷酸果糖酰基转移酶（GFPT1）调控鼻咽癌细胞对放疗的敏感度。本项目针对鼻咽癌放疗后局部复发和远处转移的问题，通过调控ebv-miR-BART7的表达来增加肿瘤细胞对放射治疗的敏感性。本项目阐明ebv-miR-BART7通过抑制GFPT1增强鼻咽癌细胞对放射治疗的敏感性，为临床上研发分子靶向ebv-miR-BART7和GFPT1的药物提供理论依据，为提高临床鼻咽癌放疗疗效提供基础依据。另一方面，ebv-miR-BART7可作为分子标志物用以筛选及预测放疗成效，提高鼻咽癌的治疗效率。