Conclusion
miR-181a-5p, miR-30a-5p and miR-30a-3p likely contribute to aging-associated vascular endothelial cell senescence.
Methods
We utilized expression microRNA arrays to evaluate control and senescent vascular endothelial cells in order to identify testable candidates. Bioinformatic analysis was used to select key microRNAs. These candidates were then modulated in vitro using microRNA mimics and inhibitors in endothelial cells, and senescence-associated gene expression patterns were evaluated by qPCR.
Results
Seventeen microRNAs were found to be significantly increased more than 2-fold in senescent cells. Of those, bioinformatic analysis concluded that miR-181a-5p, miR-30a-5p, miR-30a-3p, miR-100-5p, miR-21-5p, and miR-382-5p were likely associated with regulation of cellular senescence. We evaluated the potential targets of these six microRNAs by comparing them with cell-cycling and apoptosis-related genes from published mRNA transcriptional array data from aged tissues, and found that miR-181a-5p, miR-30a-5p and miR-30a-3p were enriched in overlapping targets compared with the other candidates. Modulation of these microRNAs in vascular endothelial cells revealed that over-expression of miR-30a-5p, and inhibition of both miR-30a-3p and miR-181a-5p, induced senescence.