Circ0061052 regulation of FoxC1/Snail pathway via miR-515-5p is involved in the epithelial-mesenchymal transition of epithelial cells during cigarette smoke-induced airway remodeling.
Airway remodeling
Chronic obstructive pulmonary disease
Cigarette smoke
CircRNA
Epithelial-mesenchymal transition
Journal
The Science of the total environment
ISSN: 1879-1026
Titre abrégé: Sci Total Environ
Pays: Netherlands
ID NLM: 0330500
Informations de publication
Date de publication:
01 Dec 2020
01 Dec 2020
Historique:
received:
18
03
2020
revised:
20
07
2020
accepted:
21
07
2020
pubmed:
10
8
2020
medline:
8
10
2020
entrez:
10
8
2020
Statut:
ppublish
Résumé
Circular RNA (circRNA) has been shown to be widely involved in a variety of lung diseases. Cigarette smoke (CS) may induce epithelial-mesenchymal transition (EMT) of airway remodeling in chronic obstructive pulmonary disease (COPD), however, in which the roles and mechanisms of circRNA have not been elucidated. In this study, we aimed to determine whether circ0061052 is involved in the EMT of human bronchial epithelial (HBE) cells and its potential mechanism for playing a biological role. Cigarette smoke extract (CSE) caused elevated EMT indicators and the increases of circ0061052 in HBE cells. Circ0061052 has a ring structure and is mainly present in the cytoplasm of HBE cells. We analyzed the regulatory relationship between circ0061052 and miR-515-5p using bioinformatics, a luciferase reporter gene, and qRT-PCR. We found that circ0061052 is mainly distributed in the cytoplasm and competitively binds to miR-515-5p, acting as a sponge for miR-515-5p. The luciferase reporter gene showed that miR-515-5p binds to the 3'UTR region of FoxC1 mRNA to inhibit its transcription. For HBE cells, overexpression of miR-515-5p antagonized the CSE-induced EMT. In addition, circ0061052 acts by binding miR-515-5p competitively to regulate the expression of FoxC1/Snail. When circ0061052 siRNA and miR-515-5p inhibitor were co-transfected into HBE cells, the inhibitor reversed the effect of circ0061052 siRNA on reducing EMT. Chronic exposure of mice to CS induced increases of circ0061052 levels, decreases of miR-515-5p levels, and the EMT in lung tissue, which caused dysfunction and airway obstruction. Overall, the results show that, by regulating miR-515-5p through a FoxC1/Snail regulatory axis, circ0061052 is involved in the CS-induced EMT and airway remodeling in COPD.
Identifiants
pubmed: 32768781
pii: S0048-9697(20)34710-0
doi: 10.1016/j.scitotenv.2020.141181
pii:
doi:
Substances chimiques
FOXC1 protein, human
0
Forkhead Transcription Factors
0
Foxc1 protein, mouse
0
MIRN515 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
141181Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.