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A novel murine model of combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma
- Source :
- Journal of Translational Medicine, Vol 20, Iss 1, Pp 1-9 (2022)
- Publication Year :
- 2022
- Publisher :
- BMC, 2022.
-
Abstract
- 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-β, 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.
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 20
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.597de4bff5e3445189bbc91861224d69
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12967-022-03791-z