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血管生成素是一个重要的促血管生成因子,在细胞增殖、迁移和凋亡等过程中均发挥重要作用,但其具体的分子机制尚待阐明.mi RNA是一类长约22 nt的小RNA,在转录后水平调控基因的表达,广泛参与各种生物学过程.本文探索了可直接调控血管生成素表达的mi RNA,希望为阐明血管生成素的作用机制提供线索.首先,我们利用数据库预测得到8个可能靶向结合血管生成素m RNA 3’端非编码区的mi RNA;然后,用实验方法验证它们与血管生成素的靶向关系,发现mi R-1208、mi R-196b、mi R-296、mi R-409-3p、mi R-570和mi R-641这6个mi RNA可以不同程度地抑制血管生成素的m RNA和蛋白质表达水平,但只有mi R-196b、mi R-296、mi R-409-3p和mi R-641可以直接结合血管生成素m RNA的3’端非编码区;进而,在血管内皮细胞中分别过表达这4个mi RNA,发现mi R-196b、mi R-409-3p和mi R-641可以抑制血管内皮细胞的细胞增殖,而mi R-196b、mi R-296和mi R-409-3p可以抑制血管内皮细胞的管腔形成.以上结果表明,细胞内有多个mi RNA调控血管生成素的表达,它们可能协调调节血管生成,抑或在血管生成的不同阶段发挥作用.我们的工作还为“一种m RNA可被多种micro RNA调节,而一种micro RNA可调节多种m RNA”假说提供了部分证据.
Angiogenin is an important pro-angiogenic factor that plays an important role in cell proliferation, migration and apoptosis, but its specific molecular mechanism remains to be elucidated.miRNA is a type of small RNA of about 22 nt , Regulate the expression of genes at the post-transcriptional level and participate in a wide range of biological processes.This paper explores the miRNAs that can directly regulate the expression of angiopoietin, hoping to provide clues for elucidating the mechanism of action of angiopoietin.First, we use the database to predict Eight miRNAs that could potentially target the 3 ’noncoding region of angiopoietin m RNA were obtained. Then, their targeting relationship with angiogenin was verified experimentally and mi R-1208, mi R-196b, mi Six mi RNAs, R-296, mi R-409-3p, mi R-570 and mi R-641, inhibited angiogenin m RNA and protein expression to some extent, but only mi R-196b, mi R -296, mi R-409-3p and mi R-641 could directly bind to the 3 ’non-coding region of angiogenin m RNA. Furthermore, overexpression of these four miRNAs in vascular endothelial cells revealed that mi R- 196b, mi R-409-3p and mi R-641 can inhibit the cell proliferation of vascular endothelial cells, while mi R-19 6b, mi R-296 and mi R-409-3p can inhibit lumen formation in vascular endothelial cells.The above results indicate that multiple miRNAs in the cell regulate angiogenin expression and may coordinate the angiogenesis, The different stages of angiogenesis play a role.Our work also provided some evidence for the hypothesis that m RNA can be regulated by multiple micro RNAs and that one microRNA can regulate multiple m RNAs.