Τετάρτη 12 Απριλίου 2017

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

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

RNA. 2017 Apr 10;:

Authors: Liu W, Lv C, Zhang B, Zhou Q, Cao Z

Abstract
Aggressive cancer cells gain robust tumor vascular mimicry (VM) capability which promotes tumor growth and metastasis. VE-cadherin is aberrantly overexpressed in vasculogenic cancer cells and regarded as a master gene of tumor VM. Although micro RNAs (miRNAs) play an important role in modulating tumor angiogenesis and cancer metastasis, the miRNA which 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 cells-mediated capillary-like structure 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 anti-tumor VM and anti-ovarian cancer therapy.

PMID: 28396577 [PubMed - as supplied by publisher]



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