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DNMT3A-mediated high expression of circ_0057504 promotes benzo[a]pyrene-induced DNA damage via the NONO-SFPQ complex in human bronchial epithelial cells.
- Source :
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Environment international [Environ Int] 2022 Dec; Vol. 170, pp. 107627. Date of Electronic Publication: 2022 Nov 10. - Publication Year :
- 2022
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Abstract
- Benzo[a]pyrene (B[a]P) is a class I carcinogen and hazardous environmental pollutant with genetic toxicity. Understanding the molecular mechanisms underlying genetic deterioration and epigenetic alterations induced by environmental contaminants may contribute to the early detection and prevention of cancer. However, the role and regulatory mechanisms of circular RNAs (circRNAs) in the B[a]P-induced DNA damage response (DDR) have not been elucidated. In this study, human bronchial epithelial cell lines (16HBE and BEAS-2B) were exposed to various concentrations of B[a]P, and BALB/c mice were treated with B[a]P intranasally. B[a]P exposure was found to induce DNA damage and upregulate circular RNA hsa&#95;circ&#95;0057504 (circ&#95;0057504) expression in vitro and in vivo. In addition, B[a]P upregulated TMEM194B mRNA and circ&#95;0057504 expression through inhibition of DNA methyltransferase 3 alpha (DNMT3A) expression in vitro. Modulation (overexpression or knockdown) of circ&#95;0057504 expression levels using a lentiviral system in human bronchial epithelial cells revealed that circ&#95;0057504 promoted B[a]P-induced DNA damage. RNA pull-down and western blot assays showed that circ&#95;0057504 interacted with non-POU domain-containing octamer-binding (NONO) and splicing factor proline and glutamine rich (SFPQ) proteins and regulated formation of the NONO-SFPQ protein complex. Thus, our findings indicate that circ&#95;0057504 acts as a novel regulator of DNA damage in human bronchial epithelial cells exposed to B[a]P. The current study reveals novel insights into the role of circRNAs in the regulation of genetic damage, and describes the effect and regulatory mechanisms of circ&#95;0057504 on B[a]P genotoxicity.<br />Competing Interests: 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.<br /> (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Animals
Humans
Mice
Bronchi drug effects
Bronchi metabolism
Epigenesis, Genetic
Epithelial Cells drug effects
Epithelial Cells metabolism
RNA, Circular genetics
RNA, Circular metabolism
Mice, Inbred BALB C
Benzo(a)pyrene toxicity
DNA Damage
DNA Methyltransferase 3A genetics
DNA-Binding Proteins metabolism
Lung Neoplasms chemically induced
Lung Neoplasms genetics
PTB-Associated Splicing Factor metabolism
RNA-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-6750
- Volume :
- 170
- Database :
- MEDLINE
- Journal :
- Environment international
- Publication Type :
- Academic Journal
- Accession number :
- 36399942
- Full Text :
- https://doi.org/10.1016/j.envint.2022.107627