TY  - EJOU
AU  - Zou, Xiaopan 
AU  - Sun, Meiyang 
AU  - Jiang, Xin 
AU  - Yu, Jingze 
AU  - Li, Xiaomeng 
AU  - Nie, Bingyu 

TI  - ZMIZ2/MCM3 Axis Participates in Triple-Negative Breast Cancer Progression
T2  - Oncology Research

PY  - 2026
VL  - 34
IS  - 1
SN  - 1555-3906

AB  -  <b>Objective:</b> 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. <b>Methods:</b> The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated. <i>In vitro</i> and <i>in vivo</i> 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. <b>Results:</b> 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 <i>in vitro</i> and <i>in vivo</i>. 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. <b>Conclusions:</b> 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.
KW  - Triple-negative breast cancer; zinc finger miz-type containing 2; minichromosome maintenance complex component 3; pathway enrichment analysis

DO  - 10.32604/or.2025.066662