ZNFX1 Functions as a Master Regulator of Epigenetically Induced Pathogen Mimicry and Inflammasome Signaling in Cancer.

ABSTRACT: DNA methyltransferase (DNMT) and PARP inhibitors induce a stimulator of IFN gene-dependent pathogen mimicry response (PMR) in ovarian and other cancers. In this study, we showed that combining DNMT and PARP inhibitors upregulates expression of the nucleic acid sensor NFX1-type zinc finger-containing 1 (ZNFX1) protein. ZNFX1 mediated the induction of PMR in mitochondria, serving as a gateway for stimulator of IFN gene-dependent IFN/inflammasome signaling. Loss of ZNFX1 in ovarian cancer cells promoted proliferation and spheroid formation in vitro and tumor growth in vivo. In patient ovarian cancer databases, expression of ZNFX1 was elevated in advanced stage disease, and ZNFX1 expression alone significantly correlated with an increase in overall survival in a phase III trial for patients wi

SUBMITTER: Stojanovic L 

PROVIDER: S-EPMC11968244 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature