|
|||||
|
|
Bioinformatic analysis and validation of microRNA-508-3p as a protective predictor by targeting NR4A3/MEK axis in pulmonary arterial hypertension |
|
| Authors: | Yi Ma Shu-Shu Chen Fen Jiang Ru-Yi Ma Huan-Liang Wang |
| Affiliation: | 1. Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China Contribution: Conceptualization (lead), Data curation (lead), Investigation (lead), Methodology (lead), Software (lead), Writing - original draft (lead), Writing - review & editing (lead);2. Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China Contribution: Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Validation (supporting);3. Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China Contribution: Data curation (supporting), Investigation (supporting), Methodology (supporting);4. Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China Contribution: Investigation (supporting), Methodology (supporting), Software (supporting);5. Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China |
| Abstract: | Pulmonary arterial hypertension (PAH) featured a debilitating progressive disorder. Here, we intend to determine diagnosis-valuable biomarkers for PAH and decode the fundamental mechanisms of the biological function of these markers. Two mRNA microarray profiles (GSE70456 and GSE117261) and two microRNA microarray profiles (GSE55427 and GSE67597) were mined from the Gene Expression Omnibus platform. Then, we identified the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs), respectively. Besides, we investigated online miRNA prediction tools to screen the target gene of DEMs. In this study, 185 DEGs and three common DEMs were screened as well as 1266 target genes of the three DEMs were identified. Next, 16 overlapping dysregulated genes from 185 DEGs and 1266 target gene were obtained. Meanwhile, we constructed the miRNA gene regulatory network and determined miRNA-508-3p-NR4A3 pair for deeper exploring. Experiment methods verified the functional expression of miR-508-3p in PAH and its signalling cascade. We observed that ectopic miR-508-3p expression promotes proliferation and migration of pulmonary artery smooth muscle cell (PASMC). Bioinformatic, dual-luciferase assay showed NR4A3 represents directly targeted gene of miR-508-3p. Mechanistically, we demonstrated that down-regulation of miR-508-3p advances PASMC proliferation and migration via inducing NR4A3 to activate MAPK/ERK kinase signalling pathway. Altogether, our research provides a promising diagnosis of predictor and therapeutic avenues for patients in PAH. |
| Keywords: | diagnosis biomarker NR4A3 MiR-508-3p pulmonary arterial hypertension |