Abstract
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.
Highlights
Related diseases caused by pulmonary arterial hypertension (PAH) have gradually become a serious public health problem
Some studies suggested that a variety of growth factors can be produced in the lung during hypoxic conditions to stimulate the proliferation of smooth muscle cells, elastic fibers, and collagen fibers in the inner membrane, resulting in pulmonary vascular remodeling [5, 6]
QPCR detected that PAH patient serum contained higher microRNA-146-5p expression and lower ubiquitin specific protease 3 (USP3) expression compared to the healthy volunteers (p < 0:05; Figures 1(a) and 1(b))
Summary
Related diseases caused by pulmonary arterial hypertension (PAH) have gradually become a serious public health problem. Some studies suggested that a variety of growth factors can be produced in the lung during hypoxic conditions to stimulate the proliferation of smooth muscle cells, elastic fibers, and collagen fibers in the inner membrane, resulting in pulmonary vascular remodeling [5, 6]. PAH caused by such vascular remodeling may be relevant to a number of mechanisms such as phenotypic changes of pulmonary smooth muscle cells [7, 8]. MiRNA is a kind of endogenous noncoding single-stranded RNA encoded by endogenous genes with a length of about 22 nucleotides, which plays a significant role in cell differentiation, proliferation, apoptosis, tumor occurrence, and drug efficiency [11, 12].
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