MicroRNA-146-5p Promotes Pulmonary Artery Endothelial Cell Proliferation under Hypoxic Conditions through Regulating USP3. (7th December 2021)

• Record Type: Journal Article
• Authors: Zhang, Wei; Qi, Yujuan; Wu, Bo
• Other Names: Pichini Simona Academic Editor.
• Is Part Of: Disease markers. Volume 2021(2021)
• Publication Date: 2021-12-07
• Subjects: Diagnosis -- Periodicals; Biochemical markers -- Periodicals; Pathology -- Periodicals; 616
• DOI: 10.1155/2021/3668422
• Languages: English
• ISSNs: 0278-0240

Abstract

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.