The regulatory network of miR-141 in the inhibition of angiogenesis
The regulatory network of miR-141 in the inhibition of angiogenesis
复制标题
miR-141 抑制血管生成的调控网络。
DOI：
10.1007/s10456-018-9654-1
复制
发表时间：
2019-05-01
期刊：
影响因子：
9.8
通讯作者：
Xu, Zhengping
中科院分区：
文献类型：
--
作者：
Dong, Haojie;Weng, Chunhua;Xu, Zhengping
由miR-200 a/B/c、miR-141和miR-429组成的miR-200家族是众所周知的在癌症侵袭和转移中抑制上皮向间充质转化（EMT）的家族。在miR-200家族成员中，已报道miR-200 a/B/c和miR-429抑制血管生成。然而，miR-141在血管生成中的作用仍然难以捉摸，因为在不同的癌症类型和肿瘤模型中发现了相互矛盾的结果。特别是，miR-141在血管内皮细胞中的作用尚未确定。在这项研究中，我们使用了几种体外和体内模型来证明内皮细胞中的miR-141抑制血管生成。其他机制研究表明，miR-141通过多个靶点抑制血管生成，包括NRP 1，GAB 1，CXCL 12，TGF 2和GATA 6，生物信息学分析表明，miR-141及其靶点组成了一个强大而精确的调控网络来调节血管生成。综上所述，这些数据不仅证明了miR-141的抗血管生成作用，进一步加强了miR-200家族在血管生成过程中的关键作用，而且还提供了一个有价值的癌症治疗靶点来控制血管生成和EMT，这是肿瘤生长和转移的两个重要步骤。
The miR-200 family, consisting of miR-200a/b/c, miR-141, and miR-429, is well known to inhibit epithelial-to-mesenchymal transition (EMT) in cancer invasion and metastasis. Among the miR-200 family members, miR-200a/b/c and miR-429 have been reported to inhibit angiogenesis. However, the role of miR-141 in angiogenesis remains elusive, as contradicting results have been found in different cancer types and tumor models. Particularly, the effect of miR-141 in vascular endothelial cells has not been defined. In this study, we used several in vitro and in vivo models to demonstrate that miR-141 in endothelial cells inhibits angiogenesis. Additional mechanistic studies showed that miR-141 suppresses angiogenesis through multiple targets, including NRP1, GAB1, CXCL12, TGF2, and GATA6, and bioinformatics analysis indicated that miR-141 and its targets comprise a powerful and precise regulatory network to modulate angiogenesis. Taken together, these data not only demonstrate an anti-angiogenic effect of miR-141, further strengthening the critical role of miR-200 family in the process of angiogenesis, but also provides a valuable cancer therapeutic target to control both angiogenesis and EMT, two essential steps in tumor growth and metastasis.