The lncRNA PAHRF functions as a competing endogenous RNA to regulate MST1 expression by sponging miR-23a-3p in pulmonary arterial hypertension.
Vascul Pharmacol
; 139: 106886, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34126237
ABSTRACT
BACKGROUND:
Emerging evidence has shown that long non-coding RNA (lncRNA) plays important roles in the development of pulmonary arterial hypertension (PAH). However, some new lncRNAs in patients with PAH are still lacking research. Herein, we examined the expression and role of lncRNA (pulmonary arterial hypertension related factor, PAHRF) in PAH.METHODS:
LncRNA PAHRF expression and localization were analyzed by realtime PCR and fluorescence in situ hybridization. Proliferation and apoptosis were detected by MTT, CCK-8, EDU staining, JC-1 assay, flow cytometry and western blotting. Luciferase activity assay was used to identify PAHRF/ miR-23a-3p/serine/threonine kinase 4 (STK4/MST1) interaction.RESULTS:
LncRNA PAHRF was down-regulated in both the PAs of PAH patients and hypoxic human pulmonary artery smooth muscle cells (PASMCs). The overexpression of PAHRF inhibited the proliferation and promoted the apoptosis of PASMCs. Similarly, we also found PAHRF overexpression decreased the proliferation under hypoxia condition. Knockdown of PAHRF exerted the opposite effects. Luciferase activity assay proved molecular binding between PAHRF and hsa-miR-23a-3p. Moreover, MST1 was confirmed to be the putative target gene and regulated by PAHRF/miR-23a-3p. In addition, we explored the molecular mechanism regulating the expression of miR-23a-3p, and found that lncRNA PAHRF acted as an endogenous sponge for miR-23a-3p, and silencing lncRNA PAHRF could up-regulate the expression of miR-23a-3p. On the contrary, PAHRF-overexpressing plasmid inhibited the expression of miR-23a-3p in hypoxia.CONCLUSIONS:
Our present study reveals a novel PAH regulating model that is composed of PAHRF, miR-23a-3p, and MST1. The aim of this study is probably going to provide a new explanation and give a further understanding of the occurrence of vascular remodeling in PAH from the perspective competing endogenous RNA hypothesis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
RNA Longo não Codificante
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Hipertensão Arterial Pulmonar
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Vascul Pharmacol
Assunto da revista:
ANGIOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA