应用慢病毒siRNA表达载体研究PPARδ22522;因在大肠癌分化及侵袭过程中的作用及靶基因

项目名称： 应用慢病毒siRNA表达载体研究PPARδ22522;因在大肠癌分化及侵袭过程中的作用及靶基因

项目编号： No.30801332

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 杨烈

作者单位： 四川大学

项目金额： 20万元

中文摘要： 过氧化物酶体增殖因子活化受体δPARδ#22312;大肠癌中的功能尚未阐明，本课题首次对PPARδ22312;大肠癌分化及侵袭过程中的作用及靶基因进行探索。采用慢病毒siRNA表达载体建立PPARδ31283;定沉默的大肠癌细胞株，通过电镜、MTT试验、ELISA、细胞粘附、迁移及侵袭试验、基因芯片及裸鼠移植瘤等实验，分析PPARδ27785;默对细胞分化、侵袭力及成瘤力的影响，筛选PPARδ30456;关的靶基因。结果：①PPARδ27785;默后大肠癌细胞分化更差，细胞-纤连蛋白粘附力、增殖力增强，侵袭力和迁移力无显著改变，细胞成瘤力显著升高，肿瘤分化更差；②PPARδ27785;默后大肠癌细胞中335个基因显著上调，460个基因显著下调；相关靶基因32个。其中分化相关基因(如：ANGPTL4，ADRP)显著下调，细胞增殖相关基因（如Ki67）显著上调，VEGF表达上调；③直肠癌中PPARδ39640;表达者具有更好的长期生存率。以上结果一致提示，PPARδ20855;有促进大肠癌细胞分化及抑制细胞增殖、肿瘤生长及细胞外粘附的作用，该作用与调节相关靶基因(如：ANGPTL4，ADRP、VEGF等)表达相关，PPARδ21487;能是大肠癌中的抑癌基因，是潜在的预后因子。

中文关键词： 过氧化物酶体增殖因子活化受体δ#20998;化;侵袭;大肠癌

英文摘要： The function of PPARδene in colorectal carcinogenesis is unclear. To explore the effect of PPARδn the differentiation and the malignancy of colorectal cancer and investigate the target genes of PPARδwe established the colon cancer cells with PPARδnockdown by using lentivirus-mediated RNAi technique and analyzed the changes of the cells. We found that,PPARδnockdown worsened the differentiation while enhanced the cell-fibronectin adhesion and proliferation of colon cancer cells, and promoted the growth of xenografts in nude mice, without effect on the invasion and the migration of cells. After knockdown of PPARδ335 genes were upregulated and 460 genes downregulated. Thirty two of these genes are possible targets of PPARδwhich closely relates to the differentiation, proliferation or angiogenesis (e.g. ANGPTL4，ADRP,Ki-67, VEGF) of colorectal cancer.Moreover, the expression of PPARδn rectal cancer was positively correlated to the long-term survival of patients after radical surgery. These findings strongly indicates that, PPARδay facilitate the differentiation while inhibit the extracellual adhesion, proliferation and growth of colorectal cancer, and thus may be an inhibitor of colorectal carcinogenesis. Besides, PPARδay be a potential prognostic factor for the colorectal cancer patients.

英文关键词： PPARδ65292;differentiation; malignancy; colorectal cancer