Role of microRNA-130a in the pathogeneses of obstructive sleep apnea hypopnea syndrome-associated pulmonary hypertension by targeting the GAX gene.

Abstract

Objective:The purpose of this study was to elucidate the role of microRNA-130a (miR-130a) in obstructive sleep apnea hypopnea syndrome (OSAHS)-associated pulmonary hypertension (PHT) by targeting the growth arrest-specific homeobox (GAX) gene.Methods:A total of 108 patients with OSAHS-associated PHT were recruited as the OSAHS-associated PHT group and 110 healthy individuals were randomly selected as the normal control group. Human umbilical vein endothelial cells (HUVECs) were selected and divided into the control, miR-130a mimic, mimic negative control (NC), miR-130a inhibitor, and inhibitor-NC groups. The dual luciferase reporter gene assay was used to identify the relationship between miR-130a and the GAX gene. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were applied for the relative expressions of miR-130a and the mRNA and protein expressions of GAX. Serum levels of endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), nitric oxide (NO), and super oxide dismutase (SOD) were detected. Cell apoptosis and angiogenic activity were analyzed by flow cytometry and cell tube formation assay.Results:GAX was a target gene of miR-130a. Compared with the normal control group, the relative expression of miR-130a and the serum levels of ET-1 and VEGF were increased, whereas the mRNA expression of GAX and the serum levels of NO and SOD were decreased in the OSAHS-associated PHT group. Compared with the control, mimic-NC, and inhibitor-NC groups, the relative expressions of miR-130a in the miR-130a mimic group were enhanced, whereas the expression of miR-130a in the miR-130a inhibitor group was reduced. However, the mRNA and protein expressions of GAX showed an opposite trend in the miR-130a mimic and miR-130a inhibitor groups. In comparison to the control, mimic-NC, and inhibitor-NC groups, the miR-130a mimic group had an increase of ET-1 and VEGF expressions, whereas the expressions of NO and SOD were reduced. However, the miR-130a inhibitor group exhibited an opposite trend. The apoptosis rate and tube formation number in the miR-130a mimic group were obviously increased, whereas the miR-130a inhibitor group showed an obvious decrease.Conclusion:These data provided strong evidence that miR-130a may be involved in the progression of OSAHS-associated PHT by down-regulating GAX gene.