Department of Hematology and Cell Therapy, Faculty of Medical Science, Tarbiat Modares University, Tehran, lran.
Stem Cell Technology Research Center, Tehran, Iran.
Exp Cell Res. 2018 Aug 1;369(1):11-16. doi: 10.1016/j.yexcr.2018.02.020. Epub 2018 Mar 30.
Angiogenesis is one of the essential hallmarks of cancer that is controlled by the balance between positive and negative regulators. FGFR1 signaling is crucial for the execution of bFGF-induced proliferation, migration, and tube formation of endothelial cells (ECs) and onset of angiogenesis on tumors. The purpose of this study is to identify whether or not miR-133 regulates FGFR1 expression and accordingly hypothesize if it plays a crucial role in modulating bFGF/FGFR1 activity in ECs and blocking tumor angiogenesis through targeting FGFR1. The influences of miR-133 overexpression on bFGF stimulated endothelial cells were assessed by cell growth curve, MTT assaying, tube formation, and migration assays. Forced expression of miR-133 caused significant reductions in bFGF-induced proliferation and migratory ability of ECs. MiR-133 Expression was negatively correlated with both mRNA and protein levels of FGFR1 in the transfected ECs isolated from peripheral blood. Moreover, overexpression of miR-133 drastically reduced the rate of cell division and disturbed capillary network formation of transfected ECs. These findings suggest that miR-133 plays an important function in bFGF-induced angiogenesis processes in ECs and provides a rationale for new therapeutic approaches to suppress tumor angiogenesis and cancer.
血管生成是癌症的一个基本特征，由正调控因子和负调控因子之间的平衡来控制。FGFR1 信号对于 bFGF 诱导的内皮细胞（EC）增殖、迁移和管腔形成以及肿瘤血管生成的开始至关重要。本研究的目的是确定 miR-133 是否调节 FGFR1 的表达，并假设它是否通过靶向 FGFR1 在调节 bFGF/FGFR1 活性和阻断肿瘤血管生成中发挥关键作用。通过细胞生长曲线、MTT 测定、管形成和迁移测定评估 miR-133 过表达对 bFGF 刺激的内皮细胞的影响。miR-133 的强制表达导致 bFGF 诱导的 EC 增殖和迁移能力显著降低。miR-133 的表达与从外周血分离的转染 EC 中 FGFR1 的 mRNA 和蛋白水平均呈负相关。此外，miR-133 的过表达大大降低了转染 EC 的细胞分裂率，并扰乱了其毛细血管网络的形成。这些发现表明，miR-133 在 bFGF 诱导的 EC 血管生成过程中发挥重要作用，并为抑制肿瘤血管生成和癌症的新治疗方法提供了依据。
