Open Access
ARTICLE
ZMIZ2/MCM3 Axis Participates in Triple-Negative Breast Cancer Progression
Xiaopan Zou1,2, Meiyang Sun3, Xin Jiang1, Jingze Yu2, Xiaomeng Li4,*, Bingyu Nie1,*
1 Breast and Thyroid Surgery, Jilin Province People’s Hospital, Changchun, 130021, China
2 The Key Laboratory of Molecular Epigenetic, Institute of Genetics and Cytology, Northeast Normal University, Changchun, 130024, China
3 Plastic Surgery Department, Shenzhen Art Star Medical Cosmetology Hospital, Shenzhen, 518000, China
4 KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 510182, China
* Corresponding Author: Xiaomeng Li. Email: 
; Bingyu Nie. Email: 
(This article belongs to the Special Issue: Advances in Cancer Immunotherapy)
Oncology Research https://doi.org/10.32604/or.2025.066662
Received 14 April 2025; Accepted 28 September 2025; Published online 24 November 2025
Abstract
Objective: Triple-negative breast cancer (TNBC) is highly aggressive and lacks an effective targeted therapy. This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2 (ZMIZ2) and minichromosome maintenance complex component 3 (MCM3) in TNBC progression. Methods: The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated. In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors. The regulatory relationship between ZMIZ2 and MCM3 was also explored. Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC. Results: High ZMIZ2 expression levels were associated with the malignant degree of TNBC. ZMIZ2 overexpression promoted TNBC cell proliferation, migration, and invasion; inhibited apoptosis; and induced G1 phase cell cycle arrest, whereas knockdown of ZMIZ2 had the opposite effect. ZMIZ2 directly targeted and positively regulated MCM3 expression. MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo. High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC. The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways, such as the mitogen-activated protein kinase (MAPK), mechanistic target of rapamycin (mTOR), Wnt, and Ras signaling pathways, as verified by The Cancer Genome Atlas data. Conclusions: ZMIZ2 and MCM3 were highly expressed in TNBC. ZMIZ2 promoted the development by positively regulating MCM3 expression. Key pathways, such as the Ras/MAPK, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mTOR, and Wnt signaling pathways, may be key downstream mechanisms.
Keywords
Triple-negative breast cancer; zinc finger miz-type containing 2; minichromosome maintenance complex component 3; pathway enrichment analysis
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