前列腺增生雄激素通路hub基因(SOX9-AR-NFKB1)的miRNA调控网络研究

项目名称： 前列腺增生雄激素通路hub基因(SOX9-AR-NFKB1)的miRNA调控网络研究

项目编号： No.81200550

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 何慧婵

作者单位： 广州医科大学

项目金额： 24万元

中文摘要： 前列腺增生是最常见的老年男性疾病,雄激素调控通路是参与前列腺生长发育的关键，其基因调控机制尚未阐明。我们已经运用表达芯片数据和蛋白组学数据，结合自主创新的Hub基因预测模型和miRNA芯片，发现前列腺雄激素通路hub基因的4个miRNA分子。但这些miRNA分子对前列腺激素通路的调控机制是什么？我们首次提出这些miRNA分子通过调控网络实现对hub基因表达的平衡调节，进而调控激素通路以维持前列腺正常发育。为证实该假说，本课题组已成功构建miRNA 高表达BPH-1细胞株，以miRNA调控前列腺激素通路为切入点，观察细胞生长和细胞凋亡指标，从中筛选作用较显著的细胞株，获得特异miRNA分子调控hub基因的可靠证据。进一步结合DIGE 技术及增生模型等方法，阐明miRNA分子影响前列腺增生的激素调控网络作用机制，为最终发现前列腺增生的治疗靶点和建立预防方案提供科学依据。

中文关键词： 前列腺增生；miRNA；雄激素通路；诊断模型；hub基因

英文摘要： Benign Prostatic hyperplasia is the most common disease of the old men and the androgen regulatory pathway is the key to prostate growth and development.However, the gene regulation mechanism has not been illustarted. According to the microarray data and proteomics data, we found out 4 miRNA molecules involved in the prostate androgen pathway which can regulate the expression of Hub gene by using independent innovation Hub gene prediction model and miRNA microarray. But, how there miRNA molecules regulate the prostate hormone pathway? We first proposed that these miRNAs maintain the prostate growth normally by regulating the hormone pathway as a result of the balance regulation. To prove the hypothesis ,we have successfully constructed high-expressed miRNA BPH-1 cell lines and focused on how miRNA regulate the prostate hormone pathway. We observed the growth and aopotosis index of the cells and chose the cell lines which play a significant role,then obtained the reliable evidence of how specific miRNA control the expression of Hub gene. Combined with the DIGE technology and proliferation model,we clarify the mechanism how miRNA molecules influence the hormone role in regulating the prostatic hyperplasia network, providing a scientific basis for the discovery of benign prostatic hyperplasia therapeutic targets an

英文关键词： Benigh Prostate Hyperplasia；miRNA；Androgen pathway；Diagnosis Mode；Hub Gene