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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.