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Published on: June 15, 2018
MicroRNA-146-5p Promotes Pulmonary Artery Endothelial Cell Proliferation under Hypoxic Conditions through Regulating
Wei Zhang1, Yujuan Qi2, Bo Wu3
1Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin, China.
Objective:
MicroRNAs play a pivotal role in the progression of pulmonary hypertension (PAH). Although microRNA-146-5p is specifically expressed in many diseases, but in PAH, its role remains elusive. Patients and Methods. 30 patients with PAH and 20 healthy volunteers in our hospital were enrolled, and their serum samples were extracted for the detection of microRNA-146-5p and ubiquitin specific protease 3 (USP3) expression. In addition, the interaction between microRNA-146-5p and USP3 was examined by luciferase reporting assay. Furthermore, the potential mechanism was explored by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and Western blotting experiments.
Results:
It was found that microRNA-146-5p was higher in PAH patients than in healthy volunteers. Meanwhile, in hypoxia-induced human pulmonary artery endothelial cell lines (HPAECs), microRNA-146-5p expression was dramatically downregulated while USP3 protein expression was conversely upregulated. Under hypoxic conditions, microRNA-146-5p mimics was able to prompt the growth of HPAECs. In addition, after overexpression of microRNA-146-5p, luciferase reporting assay revealed a reduced luciferase activity of the reporter gene containing the USP3 3'-untranslated region, and a reduction of USP3 protein expression was also confirmed. However, USP3 overexpression partially attenuated the impact of upregulated microRNA-146-5p on the proliferation capacity of HPAECs.
Conclusions:
MicroRNA-146-5p was able to enhance the proliferation ability of HPAEC cells under hypoxic conditions through targeting USP3, suggesting the microRNA-146-5p/USP3 axis may act as a target for PAH treatment.
Insights
MicroRNA-146-5p enhances pulmonary artery endothelial cell proliferation in pulmonary hypertension (PAH) by targeting USP3. This microRNA-146-5p/USP3 pathway presents a potential therapeutic target for PAH.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Biochemistry
Background:
- MicroRNAs are crucial in disease pathogenesis, but the role of microRNA-146-5p in pulmonary hypertension (PAH) is not well understood.
- Pulmonary hypertension is a complex disease affecting the pulmonary arteries, leading to elevated blood pressure in the lungs.
Purpose of the Study:
- To investigate the role and mechanism of microRNA-146-5p in the progression of pulmonary hypertension.
- To explore the relationship between microRNA-146-5p and ubiquitin specific protease 3 (USP3) in PAH.
Main Methods:
- Serum samples from 30 PAH patients and 20 healthy volunteers were analyzed for microRNA-146-5p and USP3 expression.
- Luciferase reporter assays, cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and Western blotting were used to examine the interaction and functional effects.
Main Results:
- MicroRNA-146-5p levels were elevated in PAH patients compared to healthy controls.
- In hypoxia-induced human pulmonary artery endothelial cells (HPAECs), microRNA-146-5p was downregulated, while USP3 protein was upregulated.
- Overexpression of microRNA-146-5p promoted HPAEC proliferation and reduced USP3 expression, indicating USP3 is a direct target.
Conclusions:
- MicroRNA-146-5p promotes HPAEC proliferation under hypoxic conditions by targeting USP3.
- The microRNA-146-5p/USP3 axis is a potential therapeutic target for treating pulmonary hypertension.
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