Abstract
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.
Highlights
The growth of a solid tumor depends on the blood vessels that provide the tumor with nutrition and oxygen [1]
We further detected the expression of miR-153 and angiopoietin 1 (ANG1) mRNA in these sample tissues using RT-qPCR, and we found that there was a consistent negative correlative trend between miR-153 and ANG1 at the protein and at the mRNA levels in breast cancer tissues (Fig. 1d, e)
We transfected the miR-153 mimics into three breast cancer cell lines (MCF7, MDA-MB-231, and HCC1937), and we found that miR-153 mimics downregulated the expression of ANG1 and decreased the secretion of ANG1 (Fig. 2g–i)
Summary
The growth of a solid tumor depends on the blood vessels that provide the tumor with nutrition and oxygen [1]. To provide the necessary components to permit rapid tumor growth, tumor cells activate the endothelial cells of preexisting blood vessels and promote their sprouting and migration toward the tumor by secreting proangiogenic factors [2,3,4,5]. ANG1 is a secreted ~ 70-KDa glycoprotein belonging to the angiopoietin family. This family contains three other members: angiopoietin 2 (ANG2), the mouse orthologue angiopoietin 3 (ANG3), and the human orthologue angiopoietin 4 (ANG4). The angiopoietin family contributes to the remodeling and maturation of novel blood vessels by interacting with its tyrosine kinase receptor, Tie, on the membrane of endothelial cells [7]. ANG2 is the natural antagonist for ANG1 [8, 9] and disrupts angiogenesis by inhibiting the phosphorylation of Tie2 [10]
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