HJV promoter analysis revealed potential HNF-1α and snail-binding sites, but functional analysis ruled out that these transcriptional regulators or promoter methylation are the cause of HJV downregulation in HCC.
Key features include metabolic alterations (induced by defects in HNF1A), oncogene-induced inflammation (activation of JAK-STAT signaling in inflammatory adenomas), and an association between activation of Wnt/β-catenin signaling and progression of HCAs in hepatocellular carcinomas.
This indicates that the preferential expression from the large surface antigen promoter in the differentiated hepatoma cell lines is probably mediated by HNF1 or an HNF1-related transcription factor.
These results indicate that inactivation of TCF1, whether sporadic or associated with MODY3, is an important genetic event in the occurrence of human liver adenoma, and may be an early step in the development of some HCCs.
We identified hepatic nuclear factor 1 (HNF1) as an important liver-specific trans-acting element for the human ACAT2 gene using the human hepatocellular carcinoma cell lines HuH7 and HepG2.
The competitive reverse transcriptional polymerase chain reaction was employed to amplify HNF-1 and vHNF-1 mRNA simultaneously and to examine their expression ratio in total RNA extracted from frozen liver tissues of 37 patients with hepatocellular carcinoma, five patients with hepatoblastoma, and 15 non-neoplastic liver tissues.
Here, we report that the combination of hepatocyte nuclear factor 1A (HNF1A), HNF4A and forkhead box protein A3 (FOXA3) synergistically reprograms hepatocellular carcinoma (HCC) cells to hepatocyte-like cells (reprogrammed hepatocytes, rHeps).
Thus, we identified a pathway in which TNFα-NF-κB signaling switches off negative regulation by suppressing HNF-1α-mediated expression of miR-194, revealing insight into the mechanisms linking inflammatory pathways, miRNA, and HCC metastasis.
It has been demonstrated that the hepatocyte nuclear factor 1 (HNF1) binding site is critical for the majority of the hepatitis B virus (HBV) large surface antigen promoter activity in differentiated hepatoma cell lines.
These results suggest that the extremely proximal promoter region of the AFP gene where glucocorticoid-responsive element and HNF-1 binding sites exist is not responsible for the re-expression of AFP in HCC.
Furthermore, among these four transcription factors, HNF-4 alpha and HNF-1 alpha expressions showed synchronism and had a close relation with HCC differentiation.
The -803 G > A SNP influenced the transcription efficiency in a hepatocarcinoma cell line as well as the binding efficiency of hepatocyte nuclear factor 1 alpha to the motif.
Among these tumors, biallelic inactivating mutations of the hepatocyte nuclear factor 1alpha (HNF1A) transcription factor have been frequently identified and in rare cases of hepatocellular carcinomas developed in noncirrhotic liver.
Expression of the same dominant negative mutant in human hepatoma HepG2 cells only partially inhibited endogenous LFB1 activity, due to stabilization of LFB1 dimers in these cells.
Further analyses revealed a key role of ERK leading to increased phosphorylation of p90-ribosomal S6 kinase (RSK) and a concomitant activation of ETS-like transcription factor-1(ELK1) and Death Receptor protein-5 (DR5) in HCC.