ARID3A Promotes Tumor Progression by Activating TNF-α/NF-κB Signaling in Dual-Phenotype Hepatocellular Carcinoma
Minjun Li1,2, Taixin Yang1, Juntao Huang1
1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People's Republic of China.
Journal of Hepatocellular Carcinoma
|November 25, 2025
Summary
ARID3A promotes aggressive dual-phenotype hepatocellular carcinoma (DPHCC) by activating the TNF-α/NF-κB pathway, enhancing tumor stemness and invasion. This finding offers a potential therapeutic target for DPHCC, a challenging cancer subtype.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Dual-phenotype hepatocellular carcinoma (DPHCC) exhibits significant tumor stemness and invasiveness.
- ARID3A is implicated as a potential regulator of tumor stemness in DPHCC.
Purpose of the Study:
- To elucidate the precise mechanisms by which ARID3A contributes to the aggressive behavior of DPHCC.
- To investigate the role of ARID3A in regulating tumor stemness and invasion in DPHCC.
Main Methods:
- In vitro functional assays and in vivo tumorigenesis models were employed.
- RNA sequencing (RNA-seq) identified ARID3A-mediated regulatory pathways.
- Experiments involving TNF-α/NF-κB axis modulation were conducted.
Main Results:
- ARID3A expression is upregulated in DPHCC and correlates with poor prognosis.
- ARID3A was found to enhance stemness features and tumor progression in vitro and in vivo.
- ARID3A activates the TNF-α-mediated NF-κB signaling pathway, promoting epithelial-mesenchymal transition and invasiveness.
Conclusions:
- ARID3A functions as an oncogene in DPHCC, driving aggressive characteristics of stem-like cells.
- The ARID3A-TNF-α/NF-κB axis is a key mediator of DPHCC aggressiveness.
- Targeting this axis presents a potential therapeutic strategy for DPHCC.
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