Endothelial cell is one critical structure of blood vessels, and irregular migration and proliferation of endothelial cell might cause progression of several vascular diseases such as atherosclerosis and restenosis. We showed that TNF-α, PDGF-bb, and IL-1β promote RNCR3 expression in a dose-dependent manner inhuman endothelial cell. RNCR3 level is higher in serum of atherosclerosis patients compared with those in control volunteers. Overexpression of RNCR3 promotes cell proliferation and three inflammatory cytokine secretion including IL-6, IL-1β, and TNF-α in endothelial cell. We illustrated that overexpression of RNCR3 inhibits miR-185-5p expression in endothelial cell. Furthermore, we indicated that miR-185-5p level is lower in the serum of patients with atherosclerosis compared with those in control volunteers. There is a negative correlation between miR-185-5p and RNCR3 expression in serum of patients with atherosclerosis. Using Targetscan, it predicted that miR-185-5p may bind to cyclin D2 and miR-185-5p is one potential target of miR-185-5p. Luciferase reporter data indicated that miR-185-5p suppresses luciferase value of wild-type cyclin D2 while it has no influence of cyclin D2 mutant. Overexpression of RNCR3 enhances cyclin D2 expression in endothelial cell. Moreover, RNCR3 induces cell growth and enhances inflammatory cytokine secretion through modulating cyclin D2 expression in endothelial cell. These results suggested that RNCR3 may serve as one new target for the treatment of atherosclerosis.
Keywords: Atherosclerosis; Cyclin D2; Endothelial cell; RNCR3; miR-185-5p.