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10.1038/srep43427

http://scihub22266oqcxt.onion/10.1038/srep43427
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suck abstract from ncbi


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pmid28230206
      Sci+Rep 2017 ; 7 (ä): 43427
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  • MiRNA-21 mediates the antiangiogenic activity of metformin through targeting PTEN and SMAD7 expression and PI3K/AKT pathway #MMPMID28230206
  • Luo M ; Tan X ; Mu L ; Luo Y ; Li R ; Deng X ; Chen N ; Ren M ; Li Y ; Wang L ; Wu J ; Wan Q
  • Sci Rep 2017[Feb]; 7 (ä): 43427 PMID28230206 show ga
  • 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 in the process of angiogenesis. However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear. Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays. In this study, miR-21 was strikingly downregulated by metformin in a time- and dose-dependent manner. miR-21 directly targeted the 3'-UTR of PTEN and SMAD7, and negatively regulated their expression. Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-?-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin's action and revealed significant promotion effects. Our study broadens our understanding of the regulatory mechanism of miR-21 mediating metformin-induced anti-angiogenic effects, providing important implications regarding the design of novel miRNA-based therapeutic strategies against angiogenesis.
  • |3' Untranslated Regions [MESH]
  • |Angiogenesis Inhibitors/*pharmacology [MESH]
  • |Cell Movement/drug effects [MESH]
  • |Cell Proliferation/drug effects [MESH]
  • |Computational Biology [MESH]
  • |Gene Expression Regulation [MESH]
  • |Genes, Reporter [MESH]
  • |Human Umbilical Vein Endothelial Cells/cytology/*drug effects/metabolism [MESH]
  • |Humans [MESH]
  • |Luciferases/genetics/metabolism [MESH]
  • |Metformin [MESH]
  • |MicroRNAs/antagonists & inhibitors/*genetics/metabolism [MESH]
  • |PTEN Phosphohydrolase/antagonists & inhibitors/*genetics/metabolism [MESH]
  • |Phosphatidylinositol 3-Kinases/genetics/metabolism [MESH]
  • |Phosphorylation/drug effects [MESH]
  • |Proto-Oncogene Proteins c-akt/genetics/metabolism [MESH]
  • |Signal Transduction [MESH]
  • |Smad7 Protein/antagonists & inhibitors/*genetics/metabolism [MESH]


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