EIF4A3 modulated circ_000999 promotes epithelial-mesenchymal transition in cadmium-induced malignant transformation through the miR-205-5p/ZEB1 axis.
Environ Int
; 186: 108656, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38621321
ABSTRACT
Cadmium (Cd) is an accumulative toxic metal which poses a serious threat to human health, even in trace amounts. One of the most important steps in the pathophysiology of lung cancer (LC) is the epithelial-mesenchymal transition (EMT). In this investigation, a cell malignant transformation model was established by exposing human bronchial epithelial cells (16HBE) to a low dose of Cd for 30 weeks, after which a highly expressed circular RNA (circ_000999) was identified. Cd-induced EMT was clearly observed in rat lungs and 16HBE cells, which was further enhanced following circ_000999-overexpression. Furthermore, upregulated EIF4A3 interacted with the parental gene AGTPBP1 to promote high expression of circ_000999. Subsequent experiments confirmed that circ_000999 could regulate the EMT process by competitively binding miR-205-5p and inhibiting its activity, consequently upregulating expression of zinc finger E-box binding protein 1 (ZEB1). Importantly, the circ_000999 expression level in LC tissues was significantly increased, exhibiting a strong correlation with EMT indicators. Overall, these findings provide a new objective and research direction for reversing lung EMT and subsequent treatment and prevention of LC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cadmium
/
MicroRNAs
/
Epithelial-Mesenchymal Transition
/
Zinc Finger E-box-Binding Homeobox 1
/
RNA, Circular
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Environ Int
Year:
2024
Document type:
Article
Affiliation country: