PUBLICATION
The role of AP2M1 in oncofetal characteristics: integrative in silico, in vitro, and in vivo analyses using zebrafish models
- Authors
- Ahn, S., Baek, S.E., Yu, Y., Kim, E.S., Myung, K., Kim, Y.H., Oh, C.K.
- ID
- ZDB-PUB-251202-10
- Date
- 2025
- Source
- European journal of medical research : (Journal)
- Registered Authors
- Keywords
- AP2M1, Development, HCC, Stemness, Zebrafish
- MeSH Terms
-
- Cell Proliferation
- Animals
- Gene Knockdown Techniques
- Liver Neoplasms*/genetics
- Liver Neoplasms*/metabolism
- Liver Neoplasms*/pathology
- Gene Expression Regulation, Neoplastic
- Wnt Signaling Pathway
- Cell Movement
- Humans
- Zebrafish
- Computer Simulation
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Hepatocellular*/genetics
- Carcinoma, Hepatocellular*/metabolism
- Carcinoma, Hepatocellular*/pathology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Adaptor Proteins, Signal Transducing*/genetics
- Adaptor Proteins, Signal Transducing*/metabolism
- Neoplastic Stem Cells/metabolism
- Neoplastic Stem Cells/pathology
- PubMed
- 41327404 Full text @ Eur J Med Res
Citation
Ahn, S., Baek, S.E., Yu, Y., Kim, E.S., Myung, K., Kim, Y.H., Oh, C.K. (2025) The role of AP2M1 in oncofetal characteristics: integrative in silico, in vitro, and in vivo analyses using zebrafish models. European journal of medical research. :.
Abstract
Hepatocellular carcinoma (HCC) requires novel therapeutic targets, and oncofetal genes offer a promising avenue. Although the adaptor protein AP2M1 is a known prognostic factor in HCC, its functional role in promoting cancer stemness remains unclear. This study investigates this role using an integrative in silico, in vitro, and in vivo approach. We combined TCGA database analysis with experiments using AP2M1 knockdown in HCC cell lines (HepG2, Hep3B) and morpholino knockdown of its homolog, ap2m1a, in zebrafish embryos. In silico analysis showed elevated AP2M1 in HCC, correlating positively with stemness markers. In vitro, AP2M1 knockdown suppressed proliferation, migration, invasion, and the expression of key stemness genes like DLK1 and NANOG. These findings were recapitulated in vivo, where ap2m1a knockdown in zebrafish impaired hepatocyte development and downregulated stemness markers. Mechanistically, AP2M1 depletion consistently suppressed the Wnt signaling pathway, evidenced by reduced AXIN2 expression across all models. Collectively, this study establishes AP2M1 as a key regulator of stemness in HCC, operating through the Wnt signaling pathway. Our findings validate AP2M1 as a promising biomarker and potential therapeutic target for HCC.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping