Kuehbacher Angelika, Urbich Carmen, Dimmeler Stefanie
Molecular Cardiology, Internal Medicine III, University of Frankfurt, 60590 Frankfurt, Germany.
Trends Pharmacol Sci. 2008 Jan;29(1):12-5. doi: 10.1016/j.tips.2007.10.014. Epub 2007 Dec 18.
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the post-transcriptional level by either degradation or translational repression of a target mRNA. More than 400 miRNAs have been identified in the human genome, but the relevance of most of them to physiological and pathological processes remains unclear. Although downregulation of the miRNA-processing enzymes Dicer and Drosha is known to impair angiogenesis, only a few specific miRNAs targeting endothelial cell function and angiogenesis have been identified. miR-221 and miR-222 block endothelial cell migration, proliferation and angiogenesis in vitro by targeting the stem cell factor receptor c-Kit and indirectly regulating expression of endothelial nitric oxide synthase. A pro-angiogenic function has been established for the miR-17-92 cluster, which promotes tumor angiogenesis in vivo. Expression of let7-f and miR-27b contributes to in vitro angiogenesis. We review recent studies on the involvement of miRNA in angiogenesis and discuss their implications for miRNA-based therapeutic strategies targeting this process in disease.
微小RNA(miRNA)是一类小的非编码RNA,通过降解靶mRNA或抑制其翻译在转录后水平调控基因表达。人类基因组中已鉴定出400多种miRNA,但它们大多数与生理和病理过程的相关性仍不清楚。虽然已知miRNA加工酶Dicer和Drosha的下调会损害血管生成,但仅鉴定出少数几种靶向内皮细胞功能和血管生成的特定miRNA。miR-221和miR-222通过靶向干细胞因子受体c-Kit并间接调节内皮型一氧化氮合酶的表达,在体外阻断内皮细胞迁移、增殖和血管生成。已证实miR-17-92簇具有促血管生成功能,其可在体内促进肿瘤血管生成。let7-f和miR-27b的表达有助于体外血管生成。我们综述了miRNA参与血管生成的最新研究,并讨论了它们对针对疾病中这一过程的基于miRNA的治疗策略的意义。