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

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Abstract

Aims

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)-α-mediated endothelial cell injury. The aim of the present study was to investigate the role of microRNAs in TNF-α-induced endothelial cell apoptosis.

Methods and results

Microarrays were used to analyse the global expression of microRNAs in TNF-α-stimulated human primary endothelial cells. Expression profiles of the microRNAs were verified using qRT-PCR. After TNF-α 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-α-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 kinase 4, and its related signalling caspase-3 after TNF-α treatment; however, neither pre-miR-23a nor LNA-anti-miR-23a had an effect on TNF-α-induced Bcl-2 activation.

Conclusion

Our results suggest that miR-23a may be involved in TNF-α-induced endothelial cell apoptosis through regulation of the caspase-7 and serine/threonine kinase 4–caspase-3 pathways.

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