乙酰转移酶p300对脂肪酸合成的调控机制及其在前列腺癌治疗中的意义

项目名称： 乙酰转移酶p300对脂肪酸合成的调控机制及其在前列腺癌治疗中的意义

项目编号： No.81502190

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刚晓坤

作者单位： 吉林大学

项目金额： 18万元

中文摘要： 前列腺癌是最常见的实体肿瘤之一，但对其治疗手段有限。脂肪酸合成酶（FASN）作为脂肪酸合成的关键酶，是前列腺癌治疗的理想靶标。但对于FASN的调控尚不清晰。乙酰化转移酶p300是促进前列腺癌的增殖和进展的重要转录共激活因子，本课题组基于对p300的染色质免疫沉淀-测序的分析及预试验结果，发现p300结合于FASN启动子，启动组蛋白乙酰化，转录激活FASN的表达。本课题拟通过体内、外试验，进一步研究p300对FASN调控的分子机制，及其对脂肪酸合成和肿瘤增殖的影响。本课题有助于分析转录共激活因子与DNA之间的相互作用，及组蛋白乙酰化对基因转录的影响；有助于更深入了解前列腺癌中脂肪酸合成的调控机制；更有助于确立前列腺癌的新的治疗靶点，以更科学合理的联合药物治疗，为前列腺癌治疗提供新的思路。

中文关键词： 前列腺癌；脂肪酸合成；脂肪酸合成酶；p300；乙酰化转移酶

英文摘要： Prostate cancer is one of the most common tumors, but at present, there is no alternative therapy to improve the prognosis of the patients. Fatty acid synthase (FASN), as a key enzyme in the fatty acid synthesis, is the ideal target of prostate cancer therapy. However, the regulatory mechanism of FASN in prostate cancer is still not clear. P300 acetyltransferase plays an important role in prostate cancer. Based on the p300 CHIP-Seq data analysis and the results of preliminary test, we found that p300 bound to the FASN promoter, triggered histone acetylation, transcriptional activated FASN expression. In this study, using molecular biology technology, we will deeply study the regulation mechanism of FASN by p300, and its function on fatty acid metabolism and the proliferation of prostate cancer. This project helps to analyze the interaction between transcriptional coactivator and DNA and histone acetylation; contributes to a better understanding of the regulatory mechanisms of fatty acid synthesis in prostate cancer; more importantly helps establishment of a new therapeutic target in advanced prostate cancer and a more scientific and rational drug combination therapy for the treatment of prostate cancer.

英文关键词： prostate cancer;fatty acid synthesis;FASN;p300;acetyltransferase