What question did this study set out to answer?

To examine the role of ZNF662 in the oncogenesis of epithelial ovarian cancer and its regulatory mechanisms.

June 6, 2026Open Access

ZNF662 inhibits oncogenesis through NUPR1/p53 signaling pathway in epithelial ovarian cancer and is regulated by hsa-miR-429

Key Points

To examine the role of ZNF662 in the oncogenesis of epithelial ovarian cancer and its regulatory mechanisms.
Analyzed ZNF662 expression using bioinformatics tools and clinical tissues from TCGA, GEO, and CSIOVDB.
Conducted functional assays to assess proliferation, migration, invasion, apoptosis, and cell cycle progression.
Utilized transcriptome sequencing and dual-luciferase reporter assays to explore regulatory interactions.
ZNF662 expression was significantly downregulated in ovarian cancer tissues, correlating with advanced tumor stage and poor survival.
Functional assays demonstrated ZNF662 inhibited cancer cell proliferation and invasion while promoting apoptosis and G0/G1 cell cycle arrest.
hsa-miR-429 directly downregulated ZNF662 expression, impacting EOC malignancy and establishing a pathway axis involving NUPR1 and p53.

Abstract

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.

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