鼻咽癌是我国特色恶性肿瘤，高发于华南地区。明确鼻咽癌致病重要基因及其分子机制，对发现诊治标志物、改善鼻咽癌诊治手段和疗效，具有重大意义。本课题组前期研究利用全外显子组芯片筛选并定位了一个新的鼻咽癌易感基因KLHDC4，然而，该基因的功能及其参与鼻咽癌致癌机制尚未明确。为数不多的研究结果显示，KLHDC4可能形成典型的β-propeller三维结构，并且能够与LSD1相互作用，提示其可能参与细胞表观遗传调控。表观遗传修饰的异常是导致鼻咽癌发生发展的一个重要原因，并且初步研究提示该基因能够调控鼻咽癌细胞的迁移能力。因此，本课题拟以鼻咽癌为对象，明确易感基因KLHDC4的致病相关性及其致癌能力，进一步研究其参与细胞表观遗传调控的信号通路，揭示该基因参与鼻咽癌发生发展过程的分子机制，为筛选可用于鼻咽癌早诊、预后分析以及靶向治疗的分子标志物、研发新的诊疗手段，提供必要的理论基础。

Nasopharyngeal carcinoma (NPC) is a malignant tumor prevalent in South China. Dissecting the casual gene and the corresponding mechanisms that contribute to NPC would be essential for identifying new biomarkers for diagnosis and therapy of NPC, and thus its better outcome. Using the Illumina Infinium Human Exome Bead Chip, we recently identified a novel susceptibility gene, KLHDC4, to be associated with NPC risk. However, Its functions and the mechanism involved in NPC have yet to be defined. Among a few investigations for KLHDC4, it was reported as a protein likely with typical β-propeller structure, and interacted with LSD1, suggesting its involvement in epigenetic regulation. Abnormal epigenetic modification has been known to be an important factor leading to NPC pathogenesis, and our preliminary results suggested that it can modulate the migration ability of NPC cells. Therefore, this study aims to characterize the oncogenic capacity of KLHDC4 and its related signaling pathways involved in epigenetic regulation in NPC. By revealing the molecular mechanism underlying KLHDC4 and NPC pathogenesis, we will provide more insights to the identification of biomarker for early diagnosis, prognosis and targeted therapy as well as the development of novel diagnostic and therapeutic strategies for NPC.