Effects of down-regulation of microRNA-23a on TNF-α-induced endothelial cell apoptosis through caspase-dependent pathways

Endothelial cell injury induced by inflammatory factors plays a critical role in the pathogenesis of numerous vascular diseases. MicroRNAs are well known to be implicated in cell proliferation and apoptosis in inflammatory responses; however, it remains to be determined whether microRNAs are associated with tumour necrosis factor (TNF)--mediated endothelial cell injury. The aim of the present study was to investigate the role of microRNAs in TNF--induced endothelial cell apoptosis. Microarrays were used to analyse the global expression of microRNAs in TNF--stimulated human primary endothelial cells. Expression profiles of the microRNAs were verified using qRT-PCR. After TNF- treatment, 12 miRNAs were dramatically up-regulated and nine were down-regulated. LNA-anti-miR-23a and pre-miR-23a were found to modulate one of the markedly down-regulated miRNAs, miR-23a, which could in turn increase or attenuate TNF--induced endothelial cell apoptosis. Bioinformatics analysis suggested that caspase-7 and serine/threonine kinase 4 are potential targets of miR-23a. LNA-anti-miR-23a enhanced but pre-miR-23a inhibited the activation of caspase-7, serine/threonine kinase4, and its related signalling caspase-3 after TNF- treatment; however, neither pre-miR-23a nor LNA-anti-miR-23a had an effect on TNF--induced Bcl-2 activation. Our results suggest that miR-23a may be involved in TNF--induced endothelial cell apoptosis through regulation of the caspase-7 and serine/threonine kinase4caspase-3 pathways.