N-Myc and STAT Interactor is an Endometriosis Suppressor

Authors

Yuri Park
Xiaoming Guan
Sang Jun Han

Publication Date

7-26-2024

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms25158145

PMID

39125716

PMCID

PMC11312104

PubMedCentral® Posted Date

7-26-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Female, Humans, Mice, Apoptosis, Cell Adhesion, Cell Proliferation, Endometriosis, Endometrium, Interferons, Intracellular Signaling Peptides and Proteins, Signal Transduction, Stromal Cells, ERβ, NMI, HDAC8, apoptosis, necroptosis

Abstract

In patients with endometriosis, refluxed endometrial fragments evade host immunosurveillance, developing into endometriotic lesions. However, the mechanisms underlying this evasion have not been fully elucidated. N-Myc and STAT Interactor (NMI) have been identified as key players in host immunosurveillance, including interferon (IFN)-induced cell death signaling pathways. NMI levels are markedly reduced in the stromal cells of human endometriotic lesions due to modulation by the Estrogen Receptor beta/Histone Deacetylase 8 axis. Knocking down NMI in immortalized human endometrial stromal cells (IHESCs) led to elevated RNA levels of genes involved in cell-to-cell adhesion and extracellular matrix signaling following IFNA treatment. Furthermore, NMI knockdown inhibited IFN-regulated canonical signaling pathways, such as apoptosis mediated by Interferon Stimulated Gene Factor 3 and necroptosis upon IFNA treatment. In contrast, NMI knockdown with IFNA treatment activated non-canonical IFN-regulated signaling pathways that promote proliferation, including β-Catenin and AKT signaling. Moreover, NMI knockdown in IHESCs stimulated ectopic lesions' growth in mouse endometriosis models. Therefore, NMI is a novel endometriosis suppressor, enhancing apoptosis and inhibiting proliferation and cell adhesion of endometrial cells upon IFN exposure.

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