ZEB2基因3’UTR区SNPs与非小细胞肺癌放射敏感性的相关性及机制研究

项目名称： ZEB2基因3’UTR区SNPs与非小细胞肺癌放射敏感性的相关性及机制研究

项目编号： No.81402520

项目类型： 青年科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李爱琳

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： 放射治疗是NSCLC的主要治疗手段，寻找预测其放射敏感性的分子标记，是实现个体化治疗的关键。我们发现NSCLC中ZEB2上调可以诱导EMT并降低放射敏感性。已知miRNA-200c可通过与ZEB2 mRNA的3’UTR结合显著抑制其表达，然而我们却发现部分miRNA-200c高表达的NSCLC标本中ZEB2表达反而上调。以往的研究结果证实ZEB2-3’UTR区的miRNA-200c结合位点的单碱基变异可导致ZEB2上调，且生物信息学预测发现结合位点区某些SNPs可能具有影响结合的功能。因此，我们拟进一步探讨ZEB2-3’UTR区SNPs与NSCLC放射敏感性的关系，明确其在放射敏感性差异中的作用；探寻它们影响miR-200c与ZEB2 mRNA结合，使miRNA-200c失去对ZEB2的抑制作用，从而诱导EMT进而降低放射敏感性的内在机制；试图为NSCLC放射敏感性预测提供新的分子标记。

中文关键词： 单核苷酸多态；锌指增强子结合蛋白-2；3；'端非翻译区；放射敏感性；非小细胞肺癌

英文摘要： Radiotherapy is the main treatment for NSCLC. Looking for molecular markers to predict the radiosensitivity is the key to realize the individualized treatment. We found that upregulation of ZEB2 can induce EMT and reduce the radiosensitivity in NSCLC samples. As we all know that miRNA-200c binds to the 3 'UTR of ZEB2 mRNA and inhibits its expression. However, we found that some samples with high expression of miRNA-200c showed ZEB2 expression upregulation instead. Previous research results found that single base variation at miRNA-200c binding sites in the 3 'UTR of ZEB2 can upregulate its expression, and bioinformatics prediction demonstrated that some SNPs at the binding cites may have effect on their function of binding. On this basis, we intend to study the correlations and clarify the roles of ZEB2-3 'UTR SNPs to NSCLC radiosensitivity, further to testify the process that SNPs change these binding site, then to break the inhibition role of miRNA-200c to ZEB2, further to induce EMT and reduce radiosensitivity, at last try to provide new molecular marker to NSCLC radiosensitivity.

英文关键词： single nucleotide polymorphisms (SNPs);ZEB2;3 'UTR;radiosensitivity;non-small cell lung cancer