MiR-486-3p/ZMIZ2调控WNT经典信号通路促进非小细胞肺癌发生和转移的机制研究

项目名称： MiR-486-3p/ZMIZ2调控WNT经典信号通路促进非小细胞肺癌发生和转移的机制研究

项目编号： No.81502498

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 雷哲

作者单位： 苏州大学

项目金额： 18万元

中文摘要： ZMIZ2最近被证实参与WNT/β-catenin信号通路下游基因的转录调控，并且其在肺癌中表达上调。它是否参与肺癌的发病及转移，以及其上调表达机制国内外未见报道。我们预实验结果发现ZMIZ2在非小细胞肺癌中显著上调，并且瞬时沉默ZMIZ2显著抑制肺癌细胞增殖和迁移，预示ZMIZ2在肺癌发生发展中起重要作用。同时，miR-486-3p在肺癌中表达下调，且显著抑制ZMIZ2表达。本研究拟进一步研究ZMIZ2和miR-486-3p在非小细胞肺癌组织中异常表达及相互关系；利用慢病毒转染技术，建立ZMIZ2、miR-486-3p差异表达稳定株，检测细胞增殖和转移表型变化及WNT通路相关下游基因的表达；利用agomir技术在小鼠体内观察miR-486-3p沉默ZMIZ2所导致的肿瘤生长和转移能力的变化。本研究不仅有助于阐明ZMIZ2基因促进肺癌发病及转移的分子机理，也为肺癌的诊断与治疗提供新的线索。

中文关键词： C05_气管；支气管；肺肿瘤；复发与转移；WNT信号通路；微小RNA

英文摘要： ZMIZ2 was recently confirmed to be upregulated in lung cancer and implicated in the downstream transcriptional regulation of WNT/β-catenin signaling pathway. However, the machanisms of aberrant expressed ZMIZ2 involved in lung cancer is not clear. Our pre-experiment results show that the ZMIZ2 expression is significant increased in the tissues of non-small-cell lung cancer (NSCLC) patients. Transient silencing of ZMIZ2 observably inhibits the proliferation and migration of NSCLC cells, which indicates that ZMIZ2 may play an important role in the malignance and development of lung cancer. Gene microarray results shows that miR-486-3p is downregulated in lung cancer and we find it significantly suppress ZMIZ2 expression in NSCLC cells. In this study, we are going to do some more detailed exploration of clinical correlations and epigenetic mechanisms of ZMIZ2 and miR-486-3p in NSCLC. With the use of lentiviral transfection, we are going to establish the ZMIZ2 or miR-486-3p differentially expressed NSCLC cell models for further detection of expression pattern of WNT signaling pathway related genes. The animal in vivo experiments will be done to observe the effects of miR-486-3p and ZMIZ2 on tumor growth and metastasis using a new agomir technology. This project could not only help us to elucidate the molecular mechanisms of ZMIZ2 promoting tumorigenesis and development of lung cancer, but also supply new sight for the diagnosis and treatment of lung cancer.

英文关键词： lung cancer;recurrence and metastasis;WNT signaling pathway;microRNA