miR-141在6P22扩增膀胱移行癌中与E2F3/Rb信号通路交互调控机制的研究

项目名称： miR-141在6P22扩增膀胱移行癌中与E2F3/Rb信号通路交互调控机制的研究

项目编号： No.81201997

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： 李鹏超

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 6P22扩增膀胱癌恶性程度高、分化差，E2F3过表达和Rb通路失活是其发病过程中必要事件。前期研究证实此类膀胱癌组织中miR-141和miR-200c表达较非6P22扩增膀胱癌组织降低，在6P22扩增的膀胱癌细胞系TCC-SUP中分别过表达此二者后E2F3表达降低。此外，TCC-SUP细胞中过表达miR-141后CDK1、CDK2、CDK6表达均降低，P27kip1表达增高，细胞出现G0/1期阻滞，细胞增殖受到抑制。文献报道Rb失活上调ZEB1表达诱导上皮间质转化（EMT）进程，ZEB1下调miR-141和miR-200c的表达，故推测miR-141可能与E2F3/Rb信号通路交互调控此类膀胱癌的增殖、分化和侵袭。本课题拟探讨miR-141和E2F3/Rb信号通路之间的交互调控机制，筛选关键靶点，为6P22扩增膀胱癌的个性化治疗提供新的思路。

中文关键词： 膀胱癌；微小RAN；细胞周期；迁移；侵袭

英文摘要： Overexpression of E2F3 and inactivation of Rb pathway are obligate events in the development of highly malignant, invasive bladder cancer with 6P22 amplification. Preliminary study showed that expression of miR-141 and miR-200c was lower in this kind of bladder cancer tissue than in bladder cancer tissue without 6P22 amplification. Morover, reduction of CDK1, CDK2 and CDK6 was detected accompanied with increasement of P27kip1 after overexpression of miR-141; overexpresion of miR-141 also resulted in G0/1 phase arrest and inhibition of cell proliferation in TCC-SUP cell lines with 6P22 amplification. Inactivation of Rb was reported to induce epithelial-mesenchymal transition (EMT) by up-regulating ZEB1, which down-regulates the expression of miR-141 and miR-200c. According to this, miR-141 is supposed to participate in regulating proliferation, differentiation and invasion of this type of bladder cancer through interaction with E2F3 and Rb. We aim to investigate the reciprocal regulatory mechanism between miR-141 and E2F3/Rb signal pathway. We look forward to screen key targets and provide new idea to explore personalized therapy for bladder cancer with 6P22 amplification.

英文关键词： bladder cancer；microRNA；cell cycle；migration；invasion