FoxA2 represses ERß-mediated pyroptosis in endometriosis by transcriptionally inhibiting IGF2BP1.
Exp Cell Res
; 426(1): 113539, 2023 05 01.
Article
em En
| MEDLINE
| ID: mdl-36889571
ABSTRACT
BACKGROUND:
Endometriosis is a severe disease which is associated with excessive activation of pyroptosis. Our present research aimed to investigate the function of Forkhead Box A2 (FoxA2) in regulating pyroptosis in endometriosis.METHODS:
IL-1ß and IL-18 concentrations were assessed using ELISA. Cell pyroptosis was analyzed using flow cytometry. TUNEL staining was performed to determine human endometrial stromal cells (HESC) death. Moreover, ERß mRNA stability was assessed using RNA degradation assay. Finally, the binding relationships between FoxA2, IGF2BP1 and ERß were verified by dual-luciferase reporter system, ChIP, RIP and RNA pull-down assays.RESULTS:
Our results revealed that IGF2BP1 and ERß were significantly upregulated in ectopic endometrium (EC) tissues of endometriosis patients compared to that in eutopic endometrium (EU) tissues as well as IL-18 and IL-1ß levels. Loss-of-function experiments subsequently demonstrated that either IGF2BP1 knockdown or ERß knockdown could repress HESC pyroptosis. In addition, IGF2BP1 upregulation promoted the pyroptosis in endometriosis by binding to ERß and promoting ERß mRNA stability. Our further research displayed that FoxA2 upregulation suppressed HESC pyroptosis by interacting with IGF2BP1 promoter.CONCLUSION:
Our research proved that FoxA2 upregulation downregulated ERß by transcriptionally inhibiting IGF2BP1, thereby repressing pyroptosis in endometriosis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endometriose
Limite:
Female
/
Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2023
Tipo de documento:
Article