YY1负性调控c-Myc/miR-141轴参与鼻咽癌发生发展的功能和机制研究

c-Myc、miR-141被证实在鼻咽癌发生发展中发挥“瘤基因”功能。近期结果显示c-Myc能够靶向miR-141的转录调控，YY1是c-Myc一个潜在交互作用蛋白，并在鼻咽癌中发挥抑瘤功能。但YY1通过c-Myc/miR-141轴参与鼻咽癌发生发展的机制仍有待深入研究。为此，本项目拟通过系列分子生物学和细胞生物学等技术，系统研究YY1对鼻咽癌细胞增殖、周期、凋亡、运动及侵袭转移等功能的影响；证实c-Myc对miR-141转录活性和表达的靶向调控作用；确定YY1对c-Myc/miR-141轴的调控作用及角色；并通过体内外实验探讨恢复miR-141表达对YY1、c-Myc介导的鼻咽癌恶性表型及miR-141下游PTEN、p-AKT等相关分子表达的影响；最后在临床上探讨YY1、c-Myc、miR-141、PTEN、p-AKT等分子间表达的相关性及临床价值，为鼻咽癌的分子诊疗提供重要分子靶点。

c-Myc and miR-141 have been shown to play critical roles as oncogenes in the initiation and progression of nasopharyngeal carcinoma (NPC). YY1 was identified as a potential c-Myc-interacting protein and plays a tumor suppressor role in NPC based on our preliminary results. However, the function and mechanism of YY1 involved in the initiation and progression of NPC via the regulation of c-Myc/miR-141 axis remains to be further studied. Therefore, this work aims to study the effects of YY1 on proliferation, cell cycle and apoptosis, motility, invasion and metastasis of NPC cells by performing a series of molecular and cellular biological technologies, and investigate the regulatory effect of c-Myc on the transcription activity and expression of miR-141 in NPC. Then we want to further ascertain the function and role of YY1 in c-Myc/miR-141 transcription axis, and determine the effect of restoration the expression of miR-141 on YY1 and c-Myc-mediated malignant phenotype in NPC, and the effect on the expression of the miR-141 downstream key molecules, PTEN, p-AKT, etc. Finally, we plan to determine the correlation and clinical significance of YY1, c-Myc, miR-141, PTEN and p-AKT expression, and screen some critical targets for clinical diagnosis and treatment of NPC.