miR-181c-3p and -5p promotes high-glucose-induced dysfunction in human umbilical vein endothelial cells by regulating leukemia inhibitory factor

Diabetes mellitus is a chronic metabolic disease with high blood glucose level and closely related to endothelial dysfunction, an important factor in the pathogenesis of vascular changes. Several miRNAs have been reported to be altered in a diabetic environment including miR-181c. In the article, we found that the expression of miR-181c-3p and miR-181c-5p was significantly downregulated under glucose treatment in a dose-dependent manner and in peripheral blood from diabetic patients compared with healthy participants. We explored the role of miR-181c-3p and miR-181c-5p in high glucose (HG)-induced dysfunction in human umbilical vein endothelial cells (HUVECs) by regulating leukemia inhibitory factor (LIF), their potential target with binding sites in 3-UTR region, that is also closely related to glucose metabolism. In addition, miR-181c-3p and miR-181c-5p significantly enhanced HG-induced oxidative stress injury by increasing malondialdehyde (MDA) and reactive oxygen species (ROS) production and promoted HG-induced HUVECs apoptosis, confirmed by TUNEL staining. LIF partially reduced those effects by decreasing oxidative stress and inhibiting cell apoptosis. Therefore, knocking down of LIF in HUVECs by LIF siRNA transfection, significantly increased HG-induced MDA and ROS production and induced more intense HUVECs apoptosis. Our results indicate that miR-181c-3p and miR-181c-5p promote HG-induced HUVECs injury through their target LIF.