miR-99a调节靶基因PLK1和EIF2C2表达影响膀胱癌生物学行为的分子机制研究

项目名称： miR-99a调节靶基因PLK1和EIF2C2表达影响膀胱癌生物学行为的分子机制研究

项目编号： No.81202000

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 张哲

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： 膀胱癌是我国泌尿系恶性肿瘤之一，死亡率高。寻找新的治疗靶点，具有特殊的重要性和迫切性。申请者前期研究发现miR-99a在膀胱癌中较正常组织中低表达，通过生物信息学软件预测miR-99a两个重要的靶基因PLK1和EIF2C2，并检测PLK1和EIF2C2在膀胱癌中较正常组织中高表达，随着膀胱癌恶性度增加而增加。进一步抑制和过表达miR-99a实验结合Pearson相关分析显示miR-99a表达与PLK1和EIF2C2的表达负相关。在此基础上，申请者拟通过体外干预miR-99a表达观察膀胱癌细胞生物学特性的改变，揭示miR-99a在膀胱癌进展中的作用；通过生物学功能实验和动物实验证实miR-99a对靶基因EIF2C2和PLK1及其下游蛋白的调控作用，分析它们与膀胱癌细胞生物学特性的改变关系，阐明miR-99a在膀胱癌进展中的分子作用机理，为膀胱癌靶向治疗提供新的思路。

中文关键词： 膀胱癌；miR-99a；PLK1；EIF2C2；

英文摘要： Bladder cancer is one of urinary tract malignant tumors in China and it has high mortality. It is specially important and urgent to find new therapeutic targets. Applicant's preliminary study found that there was the lower miR-99a expression in bladder cancer than that in normal bladder tissue. Bioinformatics software was used to predict that PLK1 and EIF2C2 should be the target genes of miR-99a. It was detected that PLK1 and EIF2C2 had more highly expressed in bladder cancer than those in normal tissue. The expressions of PLK1 and EIF2C2 increased with the higher degree of malignant bladder cancer. Further experiments about inhibition and overexpression of miR-99a combined with the Pearson correlation analysis showed that the miR-99a expression was negatively correlated with the expression of PLK1 and EIF2C2. On this basis, the subject will be thoroughly exploring the molecular mechanism of miR-99a in bladder cancer progression. Applicants plan to observe the changes of biological characteristics of bladder cancer cells through in vitro intervention of miR-99a expression, revealing the role of miR-99a in the progression of bladder cancer. Biological functions and animal experiments were used to confirm miR-99a regulating target genes EIF2C2, PLK1 and downstream proteins of PLK1. It was analyzed that the relatio

英文关键词： bladder cancer；miR-99a；PLK1；EIF2C2；