MiR-199a inhibits the angiogenic potential of endometrial stromal cells under hypoxia by targeting HIF-1α/VEGF pathway.

Abstract

We previously reported that miR-199a suppressed the invasiveness of endometrial stromal cells (ESCs) by targeting IkappaB kinase beta (IKKβ). This study was to investigate the role of miR-199a in the angiogenic potential of ESCs under hypoxia. Forced overexpression of miR-199a in ESCs significantly attenuated its angiogenic potential under hypoxia. Moreover, miR-199a down-regulated the expression level of vascular endothelial growth factor-A (VEGF-A) in ESCs under hypoxic conditions. To delineate the mechanism by which miR-199a reduced VEGF-A production, further analysis of the target genes of miR-199a showed that miR-199a targeted both VEGF-A and Hypoxia-inducible factor (HIF)-1α in ESCs. Our findings indicate that miR-199a may attenuate the angiogenic potential of ESCs under hypoxia partly through HIF-1α/VEGF-A pathway suppression. Therefore, miR-199a may play pivotal roles in the pathogenesis of endometriosis and may become a potential therapeutic target of this disease.