lncRNAs HIF1A-AS2 facilitates the up-regulation of HIF-1α by sponging to miR-153-3p, whereby promoting angiogenesis in HUVECs in hypoxia

Publication date: December 2017
Source:Biomedicine & Pharmacotherapy, Volume 96
Author(s): Lingjuan Li, Mingyue Wang, Zhujun Mei, Wenfeng Cao, Yun Yang, Yanmei Wang, An Wen
Angiogenesis serves as an important protective mechanism against ischemic stroke, because angiogenesis promotes the generation of collateral circulation and consequently improves the blood supply to cerebral infraction areas. Long noncoding RNAs (lncRNAs), which can act as a competing endogenous RNA, mediate protein-coding gene expression by sponging miRNA. Based on previous studies, the present study hypothesized that lncRNAs HIF1A-AS2 by sponging to miR-153-3p might regulate expression of HIF-1α and its down-stream targets, thereby influencing angiogenesis in hypoxia. Permanent middle cerebral artery occlusion (pMCAO) model was established in SD rats to explore the association between angiogenesis and expression profiles of miR-153-3p and HIF-1α in infraction areas. The effect of HIF1A-AS2 on angiogenesis was investigated in an in vitro study by using human umbilical vein endothelial cells (HUVECs). Results showed that angiogenesis was induced during pMCAO. pMCAO decreased miR-153-3p RNA level in infraction areas, but increased protein levels of HIF-1α, VEGFA and Notch1. HIF1A-AS2 was up-regulated in HUVECs in hypoxia. Luciferase reporter assay indicated that HIF1A-AS2 serves as a 'sponge' to miR-153-3p, which decreased the post-transcriptional silencing of HIF-1α by miR-153-3p. This function of HIF1A-AS2 facilitated the activation of HIF-1α/VEGFA/Notch1 cascades, by which HUVECs viability, migration ability and tube formation were promoted. These results suggest an enhanced angiogenesis in HUVECs. In short, HIF1A-AS2 facilitates the up-regulation of HIF-1α by sponging to miR-153-3p, whereby promoting angiogenesis in HUVECs in hypoxia. The present study revealed an important mechanism for understanding angiogenesis in hypoxia, thus laid theoretical basis for developing new strategy for the treatment of ischemic stroke.



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