Abstract
Atherosclerosis is one of the most prevalent and important cardiac diseases, involving the heart and brain. This study aimed to explore the impacts of lncRNA Divergent to GSC induced by TGF-b family signaling (DIGIT) on vascular endothelial cells tube-formation capacity so as to reveal the potentials of DIGIT in atherosclerosis therapy. DIGIT expression in human microvascular endothelial HMEC-1 cells was silenced by transfection with shRNAs-targeted DIGIT. The effects of DIGIT silence on cell viability, migration, apoptosis, and tube formation were then assessed. Additionally, the cross-regulation between DIGIT and miR-134, and between miR-134 and Bmi-1 was detected to further reveal through which mechanism (s) DIGIT mediated HMEC-1 cells. The results showed that DIGIT silence significantly reduced cell viability, migration, tube-like structures formation, and induced apoptosis in HMEC-1 cells. DIGIT worked as a sponge for miR-134, and the anti-growth, anti-migratory, and anti-tube-formation functions of DIGIT silence on HMEC-1 cells were abolished by miR-134 suppression. Bmi-1 was a target of miR-134, and Bmi-1 upregulation abolished miR-134 overexpression-diminished cell growth, migration, and tube formation of HMEC-1 cells. Furthermore, Bmi-1 upregulation activated PI3K/AKT and Notch signaling pathways. In conclusion, our study demonstrated that lncRNA DIGIT accelerated tube formation of vascular endothelial cells through sponging miR-134. Our findings suggest that DIGIT and miR-134 may be promising molecular targets for atherosclerosis therapy.