Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Angiogenesis. 2018 Nov;21(4):849-860. doi: 10.1007/s10456-018-9630-9. Epub 2018 Jun 29.
The sprouting of endothelial cells is the first step of tumor angiogenesis. Our previous study suggests that miR-153 suppresses breast tumor angiogenesis partially through targeting hypoxia-induced factor (HIF1α). In this study, we demonstrated that miR-153 also suppresses the migration and the tube formation of endothelial cells through directly targeting angiopoietin 1 (ANG1) in breast cancer cells. There was a negative correlation between miR-153 and ANG1 levels in breast cancer. miR-153 blocked the expression and secretion of ANG1 in breast cancer cells through binding to ANG1 mRNA. Conditioned medium from the breast cancer cell, MCF7, treated with miR-153 had no effect on the proliferation of HUVECs, but significantly inhibited the migration and tube formation of HUVECs, which could be rescued by overexpression of ANG1. In addition, miR-153 also directly inhibited the proliferation and migration of MCF7 through downregulation of ANG1. These findings suggest that miR-153 suppresses the activity of tumor cells and the migration and tube formation of endothelial cells by silencing ANG1.
内皮细胞的发芽是肿瘤血管生成的第一步。我们之前的研究表明,miR-153 通过靶向缺氧诱导因子 (HIF1α) 部分抑制乳腺癌血管生成。在这项研究中,我们证明 miR-153 还通过直接靶向乳腺癌细胞中的血管生成素 1 (ANG1) 来抑制内皮细胞的迁移和管形成。乳腺癌中 miR-153 和 ANG1 水平之间存在负相关。miR-153 通过与 ANG1 mRNA 结合来阻断乳腺癌细胞中 ANG1 的表达和分泌。用 miR-153 处理的 MCF7 乳腺癌细胞的条件培养基对 HUVECs 的增殖没有影响,但显著抑制 HUVECs 的迁移和管形成,而过表达 ANG1 可挽救这种抑制作用。此外,miR-153 还通过下调 ANG1 直接抑制 MCF7 的增殖和迁移。这些发现表明,miR-153 通过沉默 ANG1 抑制肿瘤细胞的活性以及内皮细胞的迁移和管形成。