MiR-27b Suppresses Ovarian Cancer Cell VE-cadherin Expression And Tumor Vasculogenic Mimicry

Ovarian cancer is a malignant gynecological disease, due to lack of early diagnostic methods and the effective anti-ovarian cancer drugs, the five-year survival rate of the cancer patients is only 35%, becoming one of the biggest malignant diseases to threat in the life of the women. Vasculogenic mimicry plays an important role in the growth, malignant progression, and metastasis of ovarian cancer. VE-cadherin is a master gene and regarded as a marker of tumor vasculogenic mimicry. Although microRNAs(miRNAs)has been found to act more and more important role in the regulation of tumor vascular mimicry in recent years, the mi RNA responsible for regulation of VE-cadherin- mediated tumor vascular mimicry has not been reported in the literature yet.We explored the mi RNAs in regulation of VE-cadherin-mediated vascular mimicry in ovarian cancer. First of all, we analyzed the relationship between intracellular miR-27 b levels and VE-cadherin gene expression, and found that the cells with low miR-27 b levels expressed high VE-cadherin, and the cells had vasculogenic capability. On contrast, the cells expressed high miR-27 b without VE-cadherin expression had not vasculogenic mimicry ability, suggesting that miR-27 b exerts anti-tumor vasculogenic mimicry.Bioinformatics software analysis revealed that there is direct binding site between miR-27 b and the 3’-UTR of VE-cadherin,we also validated by dual luciferase report assay. Next, we performed a series experiments to demonstrate the regulatory role of miR-27 b in ovarian cancer cells-mediated tumor vasculogenic mimicry. The results showed that after transfection of ovarian cells absent in miR-27 b or with miR-27 b constructs, intracellular mRNA and protein levels of VE-cadherin were significantly reduced; meanwhile, cell proliferation, migration, invasion, and vasclogenic mimicry were also inhibited, indicating that miR-27 b belongs to a new member of anti-vasculogenesis and anti-ovarian cancer..So far, the inhibitory effects of mi R-27 b on reduction of VE-cadherin expression and inhibition of vasculogenic mimicry have not been reported in the world; hence, our study provides new strategy and target for anti-tumor vasculogenesis and anti-ovarian cancer therapy, which has certain applied value.