FoxA2 represses ERβ-mediated pyroptosis in endometriosis by transcriptionally inhibiting IGF2BP1

Ying Feng, Feng Y, Buzhen Tan, Tan B, Han Dong, Dong H, Zheng L, Liyan Zheng
Experimental cell research · 2023 · vol. 426(1) , pp. 113539 · doi:10.1016/j.yexcr.2023.113539 · PMID:36889571 · W4323322291
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The transcription factor FoxA2 suppresses ERβ-mediated pyroptosis in endometriosis by reducing IGF2BP1 expression.

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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-1β 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, ERβ mRNA stability was assessed using RNA degradation assay. Finally, the binding relationships between FoxA2, IGF2BP1 and ERβ were verified by dual-luciferase reporter system, ChIP, RIP and RNA pull-down assays. RESULTS: Our results revealed that IGF2BP1 and ERβ 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-1β levels. Loss-of-function experiments subsequently demonstrated that either IGF2BP1 knockdown or ERβ knockdown could repress HESC pyroptosis. In addition, IGF2BP1 upregulation promoted the pyroptosis in endometriosis by binding to ERβ and promoting ERβ 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 ERβ by transcriptionally inhibiting IGF2BP1, thereby repressing pyroptosis in endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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