miR-552和miR-592在结直肠肿瘤发生、发展中的功能研究

Colorectal cancer has high prevalence and mortality. Clinical outcome of therapy for this disease remaings poor due to the fact that the mechanism underlying its initiation and development is unknown，so it influences people's life seriously . Recent studies have demonstrated that miRNA plays a significant role in cancer progress as the tumor initiating and tumor supressing genes, yet in colorectal cancers, which miRNAs and what their function are still not conclusive. In our early miRNA expression micrarray profiling studies, we have found that miR-552 and miR-592 were preferentially expressed in colorectal tumor tissues in comparison with normal tissues of the same patients. The present project is designed to expand this finding and further study the function of these two miRNAs in initiation, development and matastis of colorectal cancer cells. The study will include: 1.screening the target genes of miR-552 and miR-592 by forecast and gene expression chip;2. screening the expression of the target miRNA and their target genes in different types and grades of colorectal cancers; 3. inhibiting the miRNAs and over expressing their target genes, respectively, in primary cancer cells, and studying the changes in tumor cell characteristics; 4. over expressing the miRNAs and inhibiting the target genes in primary cells of normal colorectal tissues, and studying the expression of tumor cell characteristics in normal cells; The results of these studies will allow to get insight of the function and underlying mechanism of the target miRNAs and target genes in initiation, development and matastis of colorectal cancer cells, and will provide a novel approach to the development of effective therapy.

大肠癌是一种常见高危恶性肿瘤，因对其发生和发展过程的机制尚不清楚，因此严重影响人们的生活质量。miRNA能够参与肿瘤的发生和发展，具有与原癌基因或抑癌基因相似的作用，但在大肠肿瘤中其作用机制尚少有研究。本项目前期对大肠肿瘤及正常组织进行miRNA芯片分析及Q-PCR验证，发现miR-552和miR-592在大肠肿瘤组织中特异性高表达,文献检索发现对其研究较少；本课题拟对这两个miRNA在大肠肿瘤中的作用机制进行研究，内容包括①通过靶基因预测及基因表达谱芯片筛选各miRNA的靶基因；②将 miRNA及靶基因在不同类型及分型大肠肿瘤细胞中进行表达验证；③在肿瘤细胞中分别抑制miRNA和过表达靶基因，研究肿瘤细胞特征的改变；④在大肠正常组织细胞中过表达miRNA及抑制靶基因，研究正常细胞特性改变情况。通过本项目研究，希望能阐明目标miRNA及其靶基因在大肠肿瘤细胞癌变、增殖和转移中的作用机制。

大肠癌是一种常见高危恶性肿瘤，因对其发生和发展过程的机制尚不清楚，因此严重影响人们的生活质量。miRNA能够参与肿瘤的发生和发展，具有与原癌基因或抑癌基因相似的作用，但在大肠肿瘤中其作用机制尚少有研究。本项目前期对大肠肿瘤及正常组织进行miRNA芯片分析及Q-PCR验证，发现miR-552和miR-592在大肠肿瘤组织中特异性高表达,文献检索发现对其研究较少；本课题拟对这两个miRNA在大肠肿瘤中的作用机制进行研究，内容包括①通过靶基因预测及基因表达谱芯片筛选各miRNA的靶基因；②将 miRNA及靶基因在不同类型及分型大肠肿瘤细胞中进行表达验证；③在肿瘤细胞中分别抑制miRNA和过表达靶基因，研究肿瘤细胞特征的改变；④在大肠正常组织细胞中过表达miRNA及抑制靶基因，研究正常细胞特性改变情况。通过本项目研究，找到miRNA-552、miRNA-592的靶基因，并初步揭示了miRNA通过调控各自的靶基因的表达从而参与到大肠癌发生、发展的过程及分子机制，为大肠癌的分子靶向治疗及个体化诊疗打下基础。