放射治疗是鼻咽癌的主要治疗方式之一，但肿瘤干细胞对放疗的抵抗经常导致放射治疗失败。本项目拟探讨EVI1基因对鼻咽癌干细胞活性、放疗敏感性的影响及分子机理。本项目前期研究发现EVI1基因可以调控鼻咽癌干细胞活性。同时发现，EVI1可以负性调控miR-1的表达，从而限制了miR-1对其靶标基因c-MET的降解，最终间接活化了c-MET及其下游通路。本研究据此提出假说：EVI1可通过miR-1/c-MET信号通路调控鼻咽癌干细胞活性及放疗敏感性。为验证此假说，在后续研究中，本项目将继续探讨EVI1基因对鼻咽癌放疗敏感性的影响。同时，进一步阐明EVI1如何负性调控miR-1的表达。最后，还将探讨三氧化二砷(EVI1的特异性抑制剂)在调节鼻咽癌干细胞活性及放疗敏感性中所起的作用。本项目的开展，可为探索鼻咽癌放疗抵抗机制以及探索新的治疗方法打下初步理论基础。

Radiotherapy is one of the primary treatments of nasopharyngeal carcinoma(NPC). However, the existence of cancer stem cell(CSC) often leads to the failure of radiotherapy in the treatment of NPC. The current study is aim to investigate the role of EVI1 gene in regulating CSC properties and radiation sensitivity in NPC. Our previous study demonstrated that EVI1 elevated CSC activity. In addition, EVI1 lead to activation of c-MET signaling by negatively regulating miR-1 expression. We hypothesize that EVI1 may regulate CSC activity and radiation sensitivity by modulating the miR-1/c-MET pathway in NPC. In the further study, we are going to investigate the effect of EVI1 on radiation sensitivity and clarify how EVI1 negatively regulated miR-1 expression. Last but not the least, we will further explore the role of arsenic trioxide (a specific inhibitor of EVI1) in regulating CSC activity and radiation sensitivity in NPC cells. The project is expected to present radiation tolerance mechanism and find a new treatment method of NPC.