PO-310 miRNAs in tumor-derived microvesicles promote angiogenesis and tumour cell growth

Abstract

IntroductionIntercellular communication between cells and their microenvironment is important for tumour growth. Tumor-derived microvesicles (MVs) have recently received a great deal of attention because of their ability to induce an aggressive phenotype, immune escape, angiogenesis and drug resistance through the horizontal transfer of cellular macromolecules between cancer cells. We evaluated the role of miRNAs in tumor-derived MVs on angiogenesis and tumour growth in addition to searching for its target genes.Material and methodsMVs were isolated by ultracentrifugation in A549, H460 and BEAS2B cell lines. Candidate miRNAs in MVs were selected by miRNA array. RNA sequencing with validation by Western blot was done following the treatment of MVs in HUVEC cells.Results and discussionsA549 cell-released MVs increased the tube formation in HUVEC cells more than those of H460 or BEAS2B cells. Upon miRNA array, 11 miRNAs in A549 cell-released MVs were up-regulated and 2 miRNAs were down-regulated by more than 2-fold compared to those in MVs of H460 and BEAS2B. Among them, miR-619–5 p the most significantly increased angiogenesis in endothelial cells and growth rate of cancer cells. We found that miR-619–5 p directly targeted RCAN1.4 which has the capability to inhibit endothelial cell proliferation and angiogenesis and ectopic expression of miR-619–5 p markedly decreased RCAN1.4 expression.ConclusionOur findings provide the first evidence that tumor-derived MVs can promote angiogenesis in endothelial cells and aggressive phenotype in cancer cells through the transfer of miRNAs including miR-619–5 p. Clinical validation and exploring the way of therapeutic intervention should be followed.