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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.

MicroRNA-27b functions as a new inhibitor of ovarian cancer-mediated vasculogenic mimicry through suppression of VE-cadherin expression