MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1.
MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1.
复制标题
MicroRNA-107 通过靶向 Dicer-1 促进中风后血管生成。
DOI：
10.1038/srep13316
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发表时间：
2015-08-21
影响因子：
4.6
通讯作者：
Hu B
中科院分区：
文献类型：
--
作者：
Li Y;Mao L;Gao Y;Baral S;Zhou Y;Hu B
先前的研究表明，microRNA-107（miR-107）调节肿瘤中的细胞迁移，并促进缺氧诱导因子1α（HIF1α）在缺氧条件下调节血管生成。我们发现，大鼠永久性大脑中动脉闭塞（pMCAO）后，miR-107 在缺血边界区（IBZ）强烈表达，抑制 miR-107 可以降低中风后 IBZ 的毛细血管密度。这一发现使我们推测 miR-107 可能调节中风后血管生成，因此可作为治疗靶点。我们还发现，antagomir-107（一种合成的 miR-107 抑制剂）可减少大鼠 pMCAO 后 IBZ 毛细血管的数量并增加总体梗塞体积。我们证明 miR-107 可以直接下调 Dicer-1，这是一种编码处理 microRNA (miRNA) 前体所必需的酶的基因。这导致 VEGF（血管内皮生长因子）mRNA 的翻译抑制，从而增加内皮细胞衍生的 VEGF (VEGF165/VEGF164) 的表达，导致中风后血管生成。这一过程可能是缺血引起的脑损伤的保护机制，并且 miR-107 可能用作中风治疗的新工具。
Previous studies have suggested that microRNA-107 (miR-107) regulates cell migration in tumor and promotes Hypoxia Inducible Factor 1α (HIF1α) regulated angiogenesis under hypoxia. We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary density in the IBZ after stroke. Such finding led us to hypothesize that miR-107 might regulate post-stroke angiogenesis and therefore serve as a therapeutic target. We also found that antagomir-107, a synthetic miR-107 inhibitor, decreased the number of capillaries in IBZ and increased overall infarct volume after pMCAO in rats. We demonstrated that miR-107 could directly down-regulate Dicer-1, a gene that encodes an enzyme essential for processing microRNA (miRNA) precursors. This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke. This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.