Epithelial ovarian cancer (EOC) represents the most lethal malignancy of the female reproductive system, though its etiology and pathogenesis remain incompletely characterized. The Krüppel-associated box domain zinc finger protein (KRAB-ZNF) family, the largest transcription factor family in mammals, plays critical roles in malignant tumor development and progression. This study aimed to investigate the clinical significance and molecular mechanisms of ZNF662 in EOC pathogenesis. ZNF662 expression patterns and their association with clinicopathological features and prognosis were analyzed using integrated bioinformatics (The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), CSIOVDB, Kaplan–Meier Plotter) and clinical tissue specimens. Functional impacts on proliferation, migration, invasion, apoptosis, and cell cycle progression were assessed then. Mechanistic studies delineating upstream regulators and downstream effectors employed transcriptome sequencing, dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP), and functional validation experiments. ZNF662 expression was downregulated in ovarian cancer tissues, correlating with advanced tumor stage, ascites presence, and poor overall survival. Functional assays demonstrated that ZNF662 suppressed proliferation, migration, and invasion of ovarian cancer cells while promoting apoptosis and inducing G0/G1 cell cycle arrest. Bioinformatics analysis and dual-luciferase reporter assays confirmed that hsa-miR-429 directly binds to the 3ʹ-untranslated region (UTR) of ZNF662 , downregulating its expression and promoting malignant behaviors. Transcriptomic and mechanistic validation revealed that ZNF662 transcriptionally represses NUPR1 and activates the p53 signaling pathway, thereby inhibiting the malignant phenotype of EOC. The hsa-miR-429 /ZNF662/NUPR1/p53 pathway axis critically regulates EOC pathogenesis. ZNF662 represents a promising diagnostic biomarker and therapeutic target for EOC.
Huang et al. (Thu,) studied this question.