Deletion of HNF1α in hepatocytes results in fatty liver‐related hepatocellular carcinoma in mice

Hepatocyte nuclear factor 1α (HNF1α) is a liver‐enriched transcription factor that is critical for the maintenance of hepatocyte function. Our previous studies have demonstrated the therapeutic effects of HNF1α on hepatic fibrosis and hepatocellular carcinoma (HCC) in animals. In this study, we crea...

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Bibliographic Details
Published in:FEBS letters 2017-07, Vol.591 (13), p.1947-1957
Main Authors: Ni, Qi, Ding, Kai, Wang, Ke‐Qi, He, Jin, Yin, Chuan, Shi, Jian, Zhang, Xin, Xie, Wei‐Fen, Shi, Yong‐Quan
Format: Article
Language:English
Subjects:
Animals
Carcinogenesis
Carcinoma, Hepatocellular - complications
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Gene Deletion
Gene Expression Regulation, Neoplastic
Gene Knockout Techniques
hepatocellular carcinoma
Hepatocyte Nuclear Factor 1-alpha - deficiency
Hepatocyte Nuclear Factor 1-alpha - genetics
Hepatocytes - metabolism
HNF1α
Liver Neoplasms - complications
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Male
Mice
Mice, Inbred C57BL
NAFLD
NASH
Non-alcoholic Fatty Liver Disease - complications
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Summary:Hepatocyte nuclear factor 1α (HNF1α) is a liver‐enriched transcription factor that is critical for the maintenance of hepatocyte function. Our previous studies have demonstrated the therapeutic effects of HNF1α on hepatic fibrosis and hepatocellular carcinoma (HCC) in animals. In this study, we created hepatocyte‐specific Hnf1α knockout mice using the Cre‐loxP recombination system. The knockout mice display increased fatty acid synthesis in the liver. Moreover, these mice spontaneously develop HCC through fatty liver without cirrhosis. Inflammatory cytokines, such as tumor necrosis factor α and IL‐6, are upregulated and accompanied by increased phosphorylation of Akt, p‐65 and STAT3 in the livers of HNF1α knockout mice. Our findings suggest that HNF1α plays a crucial role in hepatocyte lipid metabolism and hepatocarcinogenesis.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.12689