Upregulation of microRNA-24 causes vasospasm following subarachnoid hemorrhage by suppressing the expression of endothelial nitric oxide synthase

Abstract

MicroRNA (miR)-24 has been reported to associate with various diseases by acting on different signaling pathways. The present study aimed to elucidate the association between miR-24 expression levels and vasospasm following subarachnoid hemorrhage (SAH), and its underlying mechanism. An miR online database was searched, identifying endothelial nitric oxide synthase (NOS3) as a potential target gene of miR-24. A luciferase reporter assay performed to investigate the regulatory association between miR-24 and NOS3 revealed that miR-24 bound to the NOS3 3' untranslated region and inhibited NOS3 expression. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to investigate the miR-24 and NOS3 expression levels in samples from patients with SAH, and demonstrated a negative correlation between the two. In addition, miR-24 expression levels were increased in SAH patients with vasospasm compared with those without, whereas the opposite results were observed for NOS3. Vascular smooth muscle cells (VSMCs) transfected with an miR-24 inhibitor exhibited increased expression levels of NOS3, whereas those transfected with an miR-24 mimic or NOS3 small interfering RNA exhibited reduced expression levels of NOS3, compared with the control. These results indicated a negative regulatory association between miR-24 and NOS3. Downregulation of NOS3 may induce vasospasm following SAH, which may be due to the upregualtion of miR-24 in VSMCs.