Role of microRNA-130a in the pathogeneses of obstructive sleep apnea hypopnea syndrome-associated pulmonary hypertension by targeting the GAX gene.
|Abstract||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.|
Protective Effects of MicroRNA-126 on Human Cardiac Microvascular Endothelial Cells Against Hypoxia/Reoxygenation-Induced Injury and Inflammatory Response by Activating PI3K/Akt/eNOS Signaling Pathway.
|Publication Year Start||2017-01-01|
PMID- 28514291 OWN - NLM STAT- MEDLINE DA - 20170517 DCOM- 20170613 LR - 20170613 IS - 1536-5964 (Electronic) IS - 0025-7974 (Linking) VI - 96 IP - 20 DP - 2017 May TI - Role of microRNA-130a in the pathogeneses of obstructive sleep apnea hypopnea syndrome-associated pulmonary hypertension by targeting the GAX gene. PG - e6746 LID - 10.1097/MD.0000000000006746 [doi] AB - 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. FAU - An, Zhe AU - An Z AD - aDepartment of Cardiology, China-Japan Union Hospital of Jilin University bDepartment of Breast Surgery, The Second Hospital of Jilin University cDepartment of Molecular Biology, College of Basic Medical Sciences, Jilin University dDepartment of Respiratory Medicine, the Second Hospital of Jilin University eDepartment of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, P.R. China. FAU - Wang, Dan AU - Wang D FAU - Yang, Guang AU - Yang G FAU - Zhang, Wen-Qi AU - Zhang WQ FAU - Ren, Jin AU - Ren J FAU - Fu, Jin-Ling AU - Fu JL LA - eng PT - Journal Article PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Biomarkers) RN - 0 (Endothelin-1) RN - 0 (Homeodomain Proteins) RN - 0 (MEOX2 protein, human) RN - 0 (MIRN130 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 126.96.36.199 (Superoxide Dismutase) SB - AIM SB - IM MH - Apoptosis/physiology MH - Biomarkers/metabolism MH - Cells, Cultured MH - Down-Regulation MH - Endothelin-1/blood MH - Female MH - Homeodomain Proteins/*metabolism MH - Human Umbilical Vein Endothelial Cells/metabolism MH - Humans MH - Hypertension, Pulmonary/*complications/*metabolism MH - Male MH - MicroRNAs/antagonists & inhibitors/genetics/*metabolism MH - Middle Aged MH - Nitric Oxide/blood MH - RNA, Messenger MH - Random Allocation MH - Sleep Apnea, Obstructive/*complications/*metabolism MH - Superoxide Dismutase/blood MH - Transfection MH - Vascular Endothelial Growth Factor A/blood PMC - PMC5440128 EDAT- 2017/05/18 06:00 MHDA- 2017/06/14 06:00 CRDT- 2017/05/18 06:00 AID - 10.1097/MD.0000000000006746 [doi] AID - 00005792-201705190-00008 [pii] PST - ppublish SO - Medicine (Baltimore). 2017 May;96(20):e6746. doi: 10.1097/MD.0000000000006746.
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