Silencing of the long non-coding RNA MEG3 suppresses the apoptosis of aortic endothelial cells in mice with chronic intermittent hypoxia via downregulation of HIF-1α by competitively binding to microRNA-135a

Background: Chronic intermittent hypoxia (CIH) involves substantial cortico-hippocampal injury, causing impairments of neurocognitive, respiratory, and cardiovascular functions. Long non-coding RNA.s (lncRNAs) participate in CIH functions and development. Therefore, we explored the mechanisms involving lncRNA maternally expressed gene 3 (MEG3) regulating the aortic endothelial function of CIH mice via regulation of microRNA-135a (miR-135a) and the hypoxia-inducible factor (HIF)-1 alpha. Methods: Expression of MEG3, mi R-135a, and HIF-1 alpha CIH mice and CIH-treated cells was detected. 71.hen, the apoptosis and proliferation of the aortic endothelial cells were examined to verify whether miR-135a and HIF-1 alpha participated in CIH. Next, the interactions between MEG3, miR-135a, and HIF-1 alpha were explored. Later, the effects of MEG3/miR-135a/HIF-1 alpha on the expression of proliferation- and apoptosis-related factors and aortic injury were investigated via gain- and loss-of function studies both in vivo and in vitro. Results: MEG3 and HIF-1 alpha were highly expressed while miR-135a was poorly expressed in CIH mice and CIH-modeled cells. Moreover, miR-135a targeted HIF-1 alpha to promote cell proliferation and inhibit apoptosis. MEG3 regulated HIF-1 alpha expression by competitively binding to miR-135a. More importantly, we found that the silencing of MEG3/HIF-1 alpha and the overexpression of miR-135a inhibited the apoptosis and injury of aortic endothelial cells while promoting cell proliferation in CIH mice. Conclusions: Altogether, silencing of MEG3 suppressed the aortic endothelial injury and cell apoptosis in CIH mice by downregulating HIF-1 alpha through sponging miR-135a, providing evidence of a potential therapeutic target for CIH.