SNHG12 Promotes Angiogenesis Following Ischemic Stroke via Regulating miR-150/VEGF Pathway.

ABSTRACT

The promotion of angiogenesis is a promising therapeutic strategy for ischemic stroke. Many long noncoding RNAs (lncRNAs) are related to angiogenesis following ischemic stroke. LncRNA small nucleolar RNA host gene 12 (SNHG12) was upregulated in oxygen-glucose deprivation (OGD)-exposed primary brain microvascular endothelial cells and in microvessel from middle cerebral artery occlusion (MCAO) animal brains. However, the role and underlying mechanism of SNHG12 in ischemic stroke especially associated with angiogenesis process remain unknown. The expression of SNHG12 and miR-150 was determined in OGD-stimulated mouse brain microvascular endothelial (bEnd.3) cells. The role and mechanism of SNHG12 in the angiogenesis after ischemic stroke were investigated using gain- and loss-of function approaches both in OGD-exposed bEnd.3 cells and in MCAO mouse models. We found SNHG12 expression was elevated, whereas miR-150 reduced in OGD-exposed bEnd.3 cells. Upregulation of SNHG12 elevated, and SNHG12 knockdown suppressed the capillary-like tube formation, viability, migration, and VEGF expression in OGD-injured bEnd.3 cells. miR-150 mimic reversed, whereas anti-miR-150 further strengthened the effect of SNHG12 upregulation on the angiogenesis in bEnd.3 cells. Furthermore, we found that SNHG12 functioned as a competing endogenous RNA for miR-150 to regulate VEGF expression. Additionally, overexpression of SNHG12 improved the recovery of neurological function, reduced infarct volume and miR-150 expression, increased vascular density and VEGF expression in the infarct border zone of MCAO mice. In conclusion, SNHG12 promotes the angiogenesis following ischemic stroke via miR-150/VEGF pathway, which further clarified the mechanism of angiogenesis after ischemic stroke and provides a target for the treatment of this disease.