MiR-126 enhances VEGF expression in induced pluripotent stem cell-derived retinal neural stem cells by targeting spred-1.

Pathological retinal neovascularization (RNV) is a leading cause of vision loss in several ocular diseases; however, the underlying molecular mechanisms involved in the development of RNV remain unclear. It has been shown that microRNAs contribute to the process of angiogenesis, which has received greater attention by investigators who study the progression of RNV. In the present study, we investigated the function of miR-126 expression in retinal neural stem cells derived from induced pluripotent stem cell (IPSs) obtained from patients with RNV. During the induction process, the levels of both miR126 and vascular endothelial growth factor C (VEGF-C) gradually decreased, while the levels of spred-1 significantly increased. The existence of conserved miR-126-binding sites in spred-1 mRNA was predicted by computational algorithms, and verified by the luciferase reporter assay. The use of miR-126 mimics revealed dramatically reduced levels of spred-1, and increased levels of VEGF. When using shRNA to target spred-1, the resultant decreased levels of spred-1 were associated with significantly enhanced levels of VEGF expression. Our results demonstrate that miR-126 promotes VEGF expression in IPS cells by suppressing spred-1 expression, which contributes to angiogenesis during the progression of RNV. These findings suggest that miR-126 and spred-1 might serve as novel molecular targets for treating RNV-related ocular diseases.