癌基因Bmi1在鼻咽癌中高表达，可永生化正常鼻咽上皮细胞，促进肿瘤转移，并与鼻咽癌进展及较差的预后显著相关，但其在鼻咽癌中异常表达的分子机制尚不清楚。我们发现：在多种肿瘤细胞株中，Bmi1的mRNA和蛋白表达水平不一致；生物信息学分析发现：Bmi1 5平不一致；存在2个保守的IRES结构。将IRES基序突变后，5序突变后，的翻译活性显著下调，提示：IRES可在翻译水平调控Bmi1表达，但与IRES结合的反式作用因子(ITAFs)尚不清楚。本项目拟采用RNA亲和沉淀结合蛋白技术和质谱分析寻找与Bmi1-IRES基序结合的ITAFs；研究ITAFs对Bmi1翻译调控、正常鼻咽上皮细胞永生化和转移的影响，并在临床肿瘤标本中检测ITAFs的表达水平，分析其临床意义及与Bmi1的相关性。研究结果将阐明IRES介导的Bmi1翻译调控机制及其结合的ITAFs/ Bmi1调控网络对肿瘤发生与转移的影响，为临床防治鼻咽癌等恶性肿瘤提供新的靶标。

Nasopharyngeal carcinoma (NPC), is one of the leading malignancy in southern China and southeast Asia. Bmi-1, which immortalizes primary human nasopharyngeal epithelial cells, is overexpressed in NPC and its.upregulation strongly correlates with an invasive phenotype and poor prognosis in patients with NPC. Therefore, it is urgent to explore the molecular mechanism of Bmi1 expression in NPC. We found that the mRNA and protein levels of Bmi1 were not completely concordant, indicating that Bmi1 may be post-transcriptionally regulated. Bioinformatic analysis shows that there are two internal ribosome entry sites in the 5’-UTR of Bmi1. The translational activity of the 5’-UTR is abolished after mutation of this two IRES elements, suggesting that the IRES elements may regulate the translation initiation of Bmi1. However, the IRES-trans-acting factors (ITAFs) responsible for the cap-independent translation of Bmi1 remain to be investigated. In the present study, we plan to identify ITAFs by RNA affinity binding proteins and mass spectrometry. We then analyze the roles of ITAFs in the translational regulation of Bmi1 and how ITAFs/Bmi1 pathway affect the tumorigenesis and progression of NPC. These results would provide molecular evidence to explore new therapeutic target for NPC.