Abstract 16761: Long Non-coding RNA Meg3 Controls Endothelial Cell Function: Implications for Endothelial Aging and Senescence (Best of Basic Science Abstract)

The majority of transcribed RNA does not encode proteins, but may function as regulatory RNA. Long non-coding RNAs (lncRNAs) have been described to play an important role in many biological processes, including epigenetic regulation of gene expression. To determine the expression and functional role of lncRNAs in endothelial cells, we performed RNA deep sequencing of human umbilical venous endothelial cells (ECs). Among the highest expressed lncRNAs, we identified Meg3 (35.3±0.6 RPKM), which was increased in replicative senescent HUVECs in vitro (passage 16/17 vs 2/3, 2.9±0.99-fold). Interestingly, Meg3 is induced in the intima of aged mice and correlates with age in human hearts (p=0.016). In HUVECs, Meg3 localizes to the nucleus and is also induced by hypoxia (4.08±0.78-fold, pu003c0.05). Silencing of Meg3 using LNA-GapmeRs induced angiogenic sprouting and proliferation of endothelial cells in vitro (1.4±0.14-fold, Pu003c0.05) and repressed SA-β-galactosidase activity. Conversely, lentiviral overexpression of M...