中文摘要：

MicroRNAs（miRNAs）是一类长度约为22／it的非编码的调控性小RNA，它们在诸多的生命活动中发挥重要作用，如参与调控细胞的增殖、分化、凋亡以及肿瘤的发生发展．MicroRNA-449a／b（miR-449a／b）是脊椎动物中进化保守的miRNA，作为抑癌基因，参与了许多癌症的发生过程，但其在结肠癌中的作用尚不清楚．本文利用实时荧光定量技术研究了miR-449a／b在结肠癌组织中的表达．利用双荧光素酶报告基因检测系统及Western印迹鉴定miR-449a／b的靶基因．应用MTS法和Transwell分别检测miR-449a／b对结肠癌细胞增殖和迁移的影响．检测组蛋白乙酰化酶抑制剂曲古菌素A（trichostatinA，TSA）对结肠癌细胞中miR-449a／b表达的影响．研究结果表明：与正常结肠组织相比，miR-449a／b在结肠癌组织中低表达；miR-449a／b能够结合到FRA-1mRNA3’-非翻译区（3’untranslatedregion，3’-UTR），从而抑制结肠癌细胞HCT116内源Fra-1的表达；外源转染miR-449a／b明显抑制结肠癌细胞HCT116的增殖和迁移；并且TSA处理能够诱导结肠癌细胞HCTll6中miR-449a／b的表达．以上结果提示：miR-49a／b可能通过抑制靶基因Fra-1的表达，进而抑制结肠癌细胞的增殖和迁移．

英文摘要：

MicroRNAs （miRNAs） are a group of small, non-coding RNA molecules about 22 nucleotides to regulate a wide variety of important biological processes, including cell proliferation, differentiation, apoptosis, as well as the progression of tumors. In the present study, the expression of microRNA-449a/ b （miR-449a/b） in colon cancer samples were assayed by real-time RT-PCR. The target genes of miR- 449a/b was verified by dual-luciferase reporter assays and Western blot. The cell proliferation and migration were evaluated by MTS and Transwell assays. The effect trichostatin A （TSA）, a histone deacetylase inhibitor, on the expression of miR-449a/b was also investigated. We found that the expression of miR-449a/b was down-regulated in colon cancer tissues compared to those of the adjacent tissues. Two putative miR-449a/b binding sites within the 3＇-untranslated region （3＇-UTR） of the human FRA-1 mRNA were identified, and verified by dual-lueiferase assays in miR-449a/b transfected HCT116 cells. The transient transfection of miR-dd9a/b into HCT116 cells drastically inhibited cell proliferation and migration. The TSA treatment was able to up-regulate miR-449a/b exoression. The data suggested that miR-449a/b inhibited the proliferation and migration of colon cancer cells by targeting the 3＇-UTR of Fra-1 mRNA and suppressing its expression.