前列腺癌组织特异microRNA表达谱研究

项目名称： 前列腺癌组织特异microRNA表达谱研究

项目编号： No.30872960

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 钟惟德

作者单位： 广州医科大学

项目金额： 31万元

中文摘要： 我们利用高通量的基因芯片和蛋白组学技术，检测前列腺癌、癌旁组织、前列腺增生组织中的miRNA表达谱、mRNA表达谱、蛋白差异表达结果，初步获得中国人种前列腺癌基础分子数据集。对上述结果进行差异表达分析，发现前列腺癌有769个基因上调，675个基因下调；有17个下调表达及11个上调表达的miRNA分子；蛋白组学鉴定获得60个差异表达蛋白。通过IPA软件对mRNA差异表达基因进行分析，发现中国人种独特的5个失调通路。通过对临床样本的miRNA原位杂交，筛选到2个与临床生化复发相关的miRNA分子（miR-23b, miR-30c），并首次揭示miR-23b可对PRDX3的调控。血清ELISA检测结果表明三个蛋白（MCCC2、TRAP1、IMPDH2）的血清水平与蛋白组结果有良好相关性；IMPDH2可作为发现早期前列腺癌和评估肿瘤进展的新的血清肿瘤标志物。基于临床样本组织芯片的免疫组化也证实CD147和SOX9等基因与前列腺癌的总体生存率和生化复发相关；肿瘤去势模型则表明SOX9在去势后激活。RNAi技术证明PSMA和EF-1α21487;分别抑制肿瘤细胞生长和侵袭力，有望作为治疗靶标。

中文关键词： 前列腺癌；microRNA表达谱；组织芯片；mRNA表达谱；蛋白组学

英文摘要： We have detected the miRNA expression profile, mRNA expression profile and global protein level of the Prostate cancer(PCa) tissues, prostate benign tissue and benign prostate hyperplasia(BPH) tissues and obtained the molecular dataset of Chinese prostate cancer by using high-throughout methods of DNA Microarray and Protiomics. Compared with the results , we discovered diffenert dis-regulated genes and proteins in PCa, there were 769 up-regulated genes, 675 down-regulated genes, 17 down-regulated miRNAs and 11 up-regulated miRNAs, and 60 disregulated proteins which were confirmed by MS. The mRNA expression was analysed by IPA and we found out 5 specific dis-regulated pathways of PCa in Chinese. We used the in situ hybridization to detect the miRNA expression of clinical samples and discovered 2 miRNAs (miR-23b, miR-30c) related with the bio-chemical recurrence(BCR), firstly proposed miR-23b can directly regulate PRDX3 in PCa. The Elisa results showed that there was a good relationship between serum level and tissue level in 3 proteins (MCCC2、TRAP1、IMPDH2) and IMPDH2 could be considered as a serum biomarker of Pca which could discover the prostate cancer eariler and estimate the cancer development. The results of tissue microarray IHC showed that the CD147 and SOX9 were both related with the overall survival rate and the free-BCR survival rate. And the castration animal modle showed us SOX9 could be activated after castration treatment. RNAi targeted PSMA / EF-1αspectively inhibited the tumor cell proliferation and invasive ability.Hence, PSMA / EF-1αromised to be new therapies targets.

英文关键词： PCa;microRNA expression profile;tissue microarray; mRNA expression profile; Proteomics