miR-4632 mediates PDGF-BB-induced proliferation and antiapoptosis of human pulmonary artery smooth muscle cells via targeting cJUN.
Am J Physiol Cell Physiol
; 313(4): C380-C391, 2017 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-28701355
ABSTRACT
MicroRNAs (miRNAs) can regulate the proliferative status of pulmonary artery smooth muscle cells (PASMCs), which is a core factor modulating pulmonary vascular remodeling diseases, such as atherosclerosis and pulmonary arterial hypertension (PAH). Our previous work has shown that miR-4632, a rarely reported miRNA, is significantly downregulated in platelet-derived growth factor (PDGF)-BB-stimulated human pulmonary artery smooth muscle cells (HPASMCs), yet its cell function and the underlying molecular mechanisms remain to be elucidated. Here, we find that miR-4632 is highly expressed in HPASMCs and its expression significantly decreased in response to different stimuli. Functional studies revealed that miR-4632 inhibited proliferation and promoted apoptosis of HPASMCs but had no effects on cell contraction and migration. Furthermore, the cJUN was identified as a direct target gene of miR-4632, while knockdown of cJUN was necessary for miR-4632-mediated HPASMC proliferation and apoptosis. In addition, the downregulation of miR-4632 by PDGF-BB was found to associate with histone deacetylation through the activation of PDGF receptor/phosphatidylinositol 3'-kinase/histone deacetylase 4 signaling. Finally, the expression of miR-4632 was reduced in the serum of patients with PAH. Overall, our results suggest that miR-4632 plays an important role in regulating HPASMC proliferation and apoptosis by suppression of cJUN, providing a novel therapeutic miRNA candidate for the treatment of pulmonary vascular remodeling diseases. It also implies that serum miR-4632 has the potential to serve as a circulating biomarker for PAH diagnosis.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
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Apoptose
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Proteínas Proto-Oncogênicas c-sis
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Miócitos de Músculo Liso
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MicroRNAs
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Proteínas Quinases JNK Ativadas por Mitógeno
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Proliferação de Células
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Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article