SR-B1在肾透明细胞癌生物学行为及缺氧脂质代谢中的作用与分子机制研究

项目名称： SR-B1在肾透明细胞癌生物学行为及缺氧脂质代谢中的作用与分子机制研究

项目编号： No.81460383

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 邹泓

作者单位： 石河子大学

项目金额： 47万元

中文摘要： 越来越多的证据表明，脂代谢异常与肾透明细胞癌（ccRCC）的发生发展有密切的关系。B组1类清道夫受体（SR-B1）在HDL胆固醇代谢中起关键作用，SR-B1与HDL结合后介导的PI3K/MAPK通路活化不仅导致细胞恶性转化，而且可激活RCC相关HIF-α通路。我们前期发现ccRCC中SR-B1基因所在染色体片段扩增，SR-B1基因高表达且均与预后密切相关，ccRCC中许多错意突变基因的功能富集于脂质代谢、胆固醇转运等进程。因此，我们推测ccRCC中SR-B1高表达可引起HDL代谢异常及PI3K/MAPK通路异常活化，进而参与ccRCC的发生发展。故本课题拟在细胞、动物实验和组织水平，通过基因表达和沉默，研究SR-B1对ccRCC中HDL代谢、细胞恶性表型、HDL-SR-B1-PI3K/MAPK、HIF-α通路的影响，初步阐明SR-B1在ccRCC生物学行为中作用、分子机制及临床应用价值。

中文关键词： C12_肾；肾盂；输尿管肿瘤；肾透明细胞癌；SR-B1；HDL；信号通路

英文摘要： More and more evidence suggests that abnormal lipid metabolism was close related with renal cell carcinoma (ccRCC). Scavenger receptor class B type 1(SR-B1) gene can play a critical role in cholesterol metabolism that regulate the level of HDL, and HDL-SR-B1 mediated PI3K-Akt, MAPK pathways are important for cancer initiation and progression, PI3K-Akt also can activating HIF-α pathway that assoiated with the pathogenesis of ccRCC. In ccRCC, our study found not only the chromosome fragment that SR-B1 gene located on was amplified, but also the SR-B1 gene were high express vs normal renal tissue, and refer to bad prognosis. The function enriched for missense mutations of renal cell carcinoma focus on some lipid metabolism, cholesterol transport, etc. So we think the high ecpression of SR-B1 may play roles in HDL metabolism and progression of CCRCC. But its role in cancer biology is not as well established, so we prepare to though cell function, animal experiment and tissue array, using gene expression and silence tool to study how the SR-B1 gene effect CCRCC cell malignant phenotype, the level of cholesterol, HDL-SR-B1-PI3K/MAPK and HIF-α signal pathway, to explain their role in carcinogenesis and cholesterol metabolism of CCRCC, and the molecular mechanism of HDL-SR-B1 pathway in control of the biological behavior and lipid metabolism of clear cell renal cell carcinoma.

英文关键词： C12_kidney; renal pelvis; ureter neoplasm;clear cell renal cell carcinoma;SR-B1;HDL;signal pathway