Background
Chronic intermittent hypoxia (CIH) involves substantial cortico-hippocampal injury, causing impairments of neurocognitive, respiratory, and cardiovascular functions. Long non-coding RNAs (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)-1α.
Conclusions
Altogether, silencing of MEG3 suppressed the aortic endothelial injury and cell apoptosis in CIH mice by downregulating HIF-1α through sponging miR-135a, providing evidence of a potential therapeutic target for CIH.
Methods
Expression of MEG3, miR-135a, and HIF-1α in CIH mice and CIH-treated cells was detected. Then, the apoptosis and proliferation of the aortic endothelial cells were examined to verify whether miR-135a and HIF-1α participated in CIH. Next, the interactions between MEG3, miR-135a, and HIF-1α were explored. Later, the effects of MEG3/miR-135a/HIF-1α 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-1α were highly expressed while miR-135a was poorly expressed in CIH mice and CIH-modeled cells. Moreover, miR-135a targeted HIF-1α to promote cell proliferation and inhibit apoptosis. MEG3 regulated HIF-1α expression by competitively binding to miR-135a. More importantly, we found that the silencing of MEG3/HIF-1α 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-1α through sponging miR-135a, providing evidence of a potential therapeutic target for CIH.