miRNA changes induced by cyclic and chronic hypoxia in human Ecs

We report the results NGS based of miRNA profiling in human endothelial cells under chronic and cyclic hypoxia Solid tumor microenvironments are often subjected to various levels of hypoxia. Although regulation of gene expression has been examined extensively, most studies have focused on chronic hypoxia. The tumor microenvironment, however, experience waves of hypoxia and reoxygenation that stimulates the expression of pro-angiogenic factors that promote blood vessel formation. In this study, we examined human umbilical vascular endothelial cells (HUVECs) under waves of intermittent (cyclic hypoxia) to determine how this process compares to chronic hypoxia, and more importantly, how this influences the microRNA profiles that potentially affect the posttranscriptional regulation of angiogenic genes. The rationale for these studies is that cancer cells subjected to cyclic hypoxia appear to have increased metastatic potential and endothelial cells exhibit a higher radiation resistance and greater migration potential. This indicates that the gene regulatory networks in cyclic hypoxia may be different from chronic hypoxia. Here we examined the consequences of cyclic hypoxia on miRNA gene expression and how these changes in miRNA expression could influence angiogenesis. Using Next Generation Sequencing, our results demonstrate that cyclic hypoxia has very different effects on the miRNA networks compared to chronic hypoxia, the in silico predicted effects on the certain mRNA target genes are more similar than might be expected. More importantly, these studies indicate that identifying potential miRNAs (including hsa-miR-19a-5p) as therapeutic targets for inhibiting angiogenesis and tumor progression will require this type of physiologically relevant analysis. mRNA profiles of HUVECs exposed to cyclic and chronic chypoxia were generated by deep sequencing.