Journal
RNA
Volume 23, Issue 7, Pages 1019-1027Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.059592.116
Keywords
ovarian cancer; miR-27b; VE-cadherin; vasculogenic mimicry
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Funding
- National Natural Science Foundation of China - priority academic program development of Jiangsu Higher Education Institutions (PAPD) [81372376, 81572257]
- Collaborative Innovation Center of Hematology, Soochow University
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province
- Chinese Ministry of Science and Technology
- Natural Science Funds of Jiangsu Colleges and Universities [16KJB310015]
- Suzhou City Scientific Research Funds [SYS201418]
- Soochow University [SDY2014A22]
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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.
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