ArticleDiscover oncology2026
NAT10 drives ovarian cancer progression via NLRP3 mRNA ac4C modification.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOvarian cancer (OV) is characterized by uncontrolled malignant proliferation of ovarian tissue. N-acetyltransferase 10(NAT10) enhances mRNA stability through N4-acetylcytidine (ac4C) modification.
objectiveThis study investigates the oncogenic role of NAT10-mediated ac4C modification in OV and to identify its critical downstream target(s). MATERIALS AND
methodsNAT10 expression was profiled in 18 paired OV and adjacent normal tissues by RT-qPCR and in two OV cell lines (TOV-112D and ES-2) versus a normal control by RT-qPCR and Western blot. ac4C modification was verified by acRIP-qPCR and acRIP-qPCR. Functional assays (CCK-8, Transwell migration and invasion) assessed the impact of NAT10 knockdown. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays mapped the NAT10-NLRP3 interaction and ac4C-dependent regulation of NLRP3 3'UTR stability. Rescue experiments evaluated whether NLRP3 overexpression could reverse the phenotype caused by NAT10 silencing.
resultsNAT10 mRNA and protein were significantly up-regulated in OV tissues and cell lines (P < 0.001), with an ROC-derived AUC of 0.865 indicating robust diagnostic potential. Knockdown of NAT10 markedly reduced proliferation, migration, and invasion of OV cells. Mechanistically, NAT10 bound directly to NLRP3 mRNA and augmented ac4C modification within its 3'UTR, thereby extending NLRP3 transcript half-life. Luciferase assays confirmed that mutation of ac4C sites abolished NAT10-mediated regulation. Restoration of NLRP3 expression fully rescued the proliferative and metastatic capacity suppressed by NAT10 depletion.
conclusionsOur findings establish NAT10-mediated ac4C modification of NLRP3 mRNA as a novel epigenetic axis that accelerates OV aggressiveness.Targeting the NAT10-NLRP3 pathway may offer a promising therapeutic avenue for patients with advanced ovarian cancer.
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