Zbed3在非小细胞肺癌发生发展中的作用及分子机制的研究

项目名称： Zbed3在非小细胞肺癌发生发展中的作用及分子机制的研究

项目编号： No.81472599

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 范垂锋

作者单位： 中国医科大学

项目金额： 64万元

中文摘要： 研究发现BED锌指结构域蛋白Zbed3能通过阻碍Axin复合体功能促进NIH3T3细胞增殖。我们发现干扰Zbed3表达能抑制肺癌细胞增殖及侵袭，并下调β-catenin及p120-ctn1表达，但机制还有待研究。我们发现Zbed3在癌中定位于细胞浆及细胞核，推测其除调节β-catenin降解外，还能影响其核浆穿梭，并通过BED结构域调控细胞周期调节因子或其它潜在因子。另外Zbed3可能通过调节p120-ctn1影响E-cahderin复合体功能从而促进侵袭转移。我们拟构建Axin及Zbed3不同位点的突变体质粒，通过转染双向调控Zbed3，β-catenin及E-cahderin等的表达，利用免疫印记，免疫荧光，实时定量PCR，免疫共沉淀，染色质免疫共沉淀，MTT，Transwell，癌细胞动物移植实验等揭示Zbed3调控非小细胞肺癌发生发展的分子机制，为临床开展分子靶向治疗提供实验基础。

中文关键词： Zbed3；非小细胞肺癌；癌发生；癌进展

英文摘要： A study has shown that Zbed3 could inhibit the function of Axin-GSK3β complex and thus promote proliferation of NIH3T3 cells. We found that downregulation of Zbed3 using siRNA significantly inhibits non-small cell lung cancer (NSCLC) cell proliferation and invasion, and downregulates expression ofβ-catenin and p120ctn-1. However the mechanism involved need further study. We found Zbed3 was located in cytoplasm and nuclear of cancer cells. We assume that Zbed3 could regulate cytoplasm-nuclear shuttling of β-catenin besides its function of regulating β-catenin degradation, and it also could regulate factors regulating cell cycle or other factors through BED domain. Furthermore, we assume that Zbed3 could regulate cancer cell invasion and metastasis through regulating p120ctn-1 and consequently affecting function of E-cadherin complex. In this program we intend to investigate the molecular mechanism involved in regulation of carcinogenesis and development of NSCLC by Zbed3 through building mutants of Axin and Zbed3, Western blotting, immunofluorescence, Real-Time PCR, immunoprecipitation, Chromatin immunoprecipitation, MTT, Transwell and nude mice xenograft transplantation experiments and thus provide experimental basis for carrying out clinical treatment of NSCLC based on molecular targets of its proliferation, invasion and metastasis.

英文关键词： Zbed3;non-small cell lung cancer;carcinogenesis;cancer development