SOX7在乳腺癌中调控机制的研究

项目名称： SOX7在乳腺癌中调控机制的研究

项目编号： No.81472635

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： 隋广超

作者单位： 东北林业大学

项目金额： 72万元

中文摘要： 抑癌基因SOX7在肿瘤中低表达的机制还没有被研究透彻，癌细胞中SOX7的调控基因还未被探索。我们的前期研究表明，microRNA有调节SOX7的可能性，乳腺癌细胞中外源SOX7可改变调节细胞存活，迁移和增殖基因的表达。因此我们推测：乳腺癌中microRNA抑制SOX7的表达，SOX7调节的基因对其抑癌功能很重要。本项目拟研究以下内容：1. 利用报告载体和对内源基因表达的控制，阐明microRNA对SOX7的调节。同时，测定它们在乳腺癌中表达的相关性。2. 确定SOX7对新发现的四个潜在靶基因的控制，并研究它们对于SOX7抑癌活性的贡献和与SOX7表达的相关性。项目的创新处是，microRNA对SOX7的调控还研究甚少，SOX7调节的基因表达对其抑癌活性的作用尚未被探索。我们研究的目的是解析SOX7上下游调节的机制，为在乳腺癌治疗中激活SOX7表达或刺激其调节的抑癌通路提供理论依据。

中文关键词： C21_乳腺肿瘤；SOX7；microRNA；基因表达

英文摘要： Recent studies suggest a tumor suppressive role of SOX7 in oncogenesis. However, many gaps still exist regarding how SOX7 is regulated and whether SOX7-mediated gene transcription plays a role in the tumor suppressive activity of SOX7. In our preliminary studies, we found that SOX7 expression can be potentially regulated by microRNAs and ectopic SOX7 expression in breast cancer could significantly alter the expression of genes involved in cell death, survival, development, mobility, and proliferation. Based on these observations, we hypothesize that microRNAs play an important role in downregulating SOX7 in breast cancer; SOX7-mediated gene expression contributes to its tumor suppressive activity. Our objectives include dissecting the mechanisms of the SOX7-related regulatory network and determining the biological importance of SOX7-mediated tumor suppression in breast cancer pathogenesis. We have two specific aims to test these hypotheses. In Aim 1, we will determine the contribution of microRNAs to SOX7 downregulation in breast cancer. In this aim, we will study whether SOX7 downregulation is regulated by the microRNAs determined in our preliminary studies and examine the expression correlation of these microRNAs with SOX7 in breast cancer. In Aim 2, we will investigate SOX7 target genes and their contribution to SOX7-mediated tumor suppression. In this aim, we will validate the regulation of these candidate target genes by SOX7, assess their roles in SOX7-mediated tumor suppression, and examine their correlation with SOX7 in breast cancer. The innovation of this proposal lies in its innovative preliminary data and specific aims. We propose to study the contribution of microRNAs to SOX7 reduction, its prognostic potential, and its mediated gene expression to breast cancer oncogenesis. None of these studies have been explored previously. Our project will unravel mechanisms of both SOX7 upstream and downstream regulation, and its potential role in breast cancer prognosis. The success of this study will advance our understanding of the regulation of SOX7 as a novel tumor suppressor and provide insight into the intervention of breast cancer progression through reactivating SOX7 and its regulated tumor suppressive network.

英文关键词： breast cancer;SOX7;microRNA;gene expression