A novel murine model of combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
J Transl Med
; 20(1): 579, 2022 12 09.
Article
en En
| MEDLINE
| ID: mdl-36494846
ABSTRACT
Primary liver cancer (PLC) is a common gastrointestinal malignancy worldwide. While hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two major pathologic types of PLC, combined HCC and ICC (cHCC-ICC) is a relatively rare subtype that shares both hepatocyte and cholangiocyte differentiation. However, the molecular feature of this unique tumor remains elusive because of its low incidence and lack of a suitable animal model. Herein, we generated a novel spontaneous cHCC-ICC model using a Sleeping Beauty-dependent transposon plasmid co-expressing oncogenic Myc and AKT1 and a CRISPR-Cas9 plasmid expressing single-guide RNA targeting p53 into mouse hepatocytes via in situ electroporation. The histological and transcriptional analysis confirmed that this model exhibits cHCC-ICC features and activates pathways committing cHCC-ICC formation, such as TGF-ß, WNT, and NF-κB. Using this model, we further screened and identified LAMB1, a protein involved in cell adhesion and migration, as a potential therapeutic target for cHCC-ICC. In conclusion, our work presents a novel genetic cHCC-ICC model and provides new insights into cHCC-ICC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de los Conductos Biliares
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Colangiocarcinoma
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Transl Med
Año:
2022
Tipo del documento:
Article
País de afiliación:
China