鼻咽癌95%以上病理分化不良，恶性程度高，疗效难以进一步提高。从分子水平深入探索鼻咽癌分化障碍的关键分子，有利于开辟鼻咽癌精准治疗新途径。我们前期结果发现：①EB病毒编码miRNA-BART10在未分化型鼻咽癌中高表达，且抑制miRNA-BART10表达可促进鼻咽癌细胞向正常细胞方向分化；②诱导分化药物可抑制miR-BART10和病毒编码基因LMP1表达，干扰LMP1表达后miR-BART10表达呈同向改变，但具体机制不详。在此基础上，本项目拟开展以下研究：通过体内外实验阐明miR-BART10在鼻咽癌分化障碍中功能和作用机制；明确EB病毒编码LMP1介导miR-BART10表达的具体调控机制；在300例未分化型鼻咽癌标本中明确miR-BART10、LMP1与鼻咽癌分化障碍的临床相关性。通过本项目的实施，为鼻咽癌诱导分化治疗提供提供新靶点，开辟鼻咽癌精准治疗新途径，以进一步提高疗效。

More than 95% nasopharyngeal carcinomas (NPC) are pathologically diagnosed as undifferentiated cancers, with high malignant degree. The survival of NPC is hard to further improved. Intensive study on the molecular mechanisms of key markers in undifferentiation is an important way to identify new therapeutic strategy and improve survival in NPC. In previous study, we found that Epstein–Barr virus (EB virus) encoded miR-BART10 was overexpressed in undifferentiated NPC. Knocking down miR-BART10 expression led to NPC cell differentiation. Differentiation agent reduced expression of miR-BART10 and EB virus encoded gene LMP1. Knocking down of LMP1 expression led to miR-BART10 downregulation, while LMP1 overexpression increased miR-BART10 expression, but the regulation mechanisms remains unknown. On this basis, we intend to carry out the following researches: study the function and mechanism of miR-BART10 in NPC differentiation block in vitro and in vivo; clarify the regulation mechanism how EB virus encoded gene LMP1 mediates miR-BART10 expression; examine the clinical correlation of miR-BART10, LMP1 and downstream markers in NPC. This research will provide novel targets and compelling evidence to apply differentiation therapy as a novel therapeutic strategy for accurate therapy, to further improve survival in NPC patients.