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MicroRNA-27b functions as a new inhibitor of ovarian cancer-mediated vasculogenic
mimicry through suppression of VE-cadherin expression
#MMPMID28396577
Liu W
; Lv C
; Zhang B
; Zhou Q
; Cao Z
RNA
2017[Jul]; 23
(7
): 1019-1027
PMID28396577
show ga
Aggressive cancer cells gain robust tumor vascular mimicry (VM) capability that
promotes tumor growth and metastasis. VE-cadherin is aberrantly overexpressed in
vasculogenic cancer cells and regarded as a master gene of tumor VM. Although
microRNAs (miRNAs) play an important role in modulating tumor angiogenesis and
cancer metastasis, the miRNA that targets VE-cadherin expression in cancer cells
to inhibit tumor cell-mediated VM is enigmatic. In this study, we found that
miR-27b levels are negatively co-related to VE-cadherin expression in ovarian
cancer cells and tumor cell-mediated VM, and demonstrated that miR-27b could bind
to the 3'-untranslated region (3'UTR) of VE-cadherin mRNA. Overexpression of
miR-27b in aggressive ovarian cancer cell lines Hey1B and ES2 significantly
diminished intracellular VE-cadherin expression; convincingly, the inhibitory
effect of miR-27b could be reversed by miR-27b specific inhibitor. Intriguingly,
miR-27b not only effectively suppressed ovarian cancer cell migration and
invasion, but also markedly inhibited formation of ovarian cancer cell-mediated
capillary-like structures in vitro and suppressed generation of functional tumor
blood vessels in mice. Together, our study suggests that miR-27b functions as a
new inhibitor of ovarian cancer cell-mediated VM through suppression of
VE-cadherin expression, providing a new potential drug candidate for antitumor VM
and anti-ovarian cancer therapy.
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