MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway

• DOI: 10.1038/srep43427
• Publication Date: 2017-02-23T11:12:00Z
• Authors: Mao Luo; Xiaoyong Tan; Lin Mu; Yulin Luo; Rong Li; Xin Deng; Ni Chen; Meiping Ren; Yongjie Li; Liqun Wang; Jianbo Wu; Qin Wan
• Keywords: Biguanide

Abstract Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with anti-angiogenic effects in conditions beyond diabetes. miR-21 has been reported to be involved the process of angiogenesis. However, precise regulatory mechanisms by which metformin-induced endothelial suppression and its on miR-21-dependent pathways are still unclear. Bioinformatic analysis identification targets their antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch CCK-8 assays tubule formation assays. In this study, was strikingly downregulated metformin a time- dose-dependent manner. directly targeted 3′-UTR PTEN SMAD7, negatively regulated expression. Overexpression abrogated metformin-mediated inhibition cells proliferation, migration, TGF-β-induced AKT, SMAD- ERK-dependent phosphorylations, conversely, down-regulation aggravated metformin’s action revealed significant promotion effects. Our study broadens our understanding mechanism mediating effects, providing important implications regarding design novel miRNA-based therapeutic strategies against