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A novel murine model of combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma.


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.

SUBMITTER: Xu RC 

PROVIDER: S-EPMC9733131 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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A novel murine model of combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

Xu Ru-Chen RC   Wang Fu F   Sun Jia-Lei JL   Abuduwaili Weinire W   Zhang Guang-Cong GC   Liu Zhi-Yong ZY   Liu Tao-Tao TT   Dong Ling L   Shen Xi-Zhong XZ   Zhu Ji-Min JM  

Journal of translational medicine 20221209 1


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-  ...[more]

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