Transcriptional regulation of the human transferrin gene by GADD153 in hepatoma cells

Hepatology ◽  
2003 ◽  
Vol 38 (3) ◽  
pp. 745-755 ◽  
Author(s):  
K You
1994 ◽  
Vol 269 (39) ◽  
pp. 24504-24510
Author(s):  
A. Espinosa de los Monteros ◽  
B.E. Sawaya ◽  
F. Guillou ◽  
M.M. Zakin ◽  
J. de Vellis ◽  
...  

Author(s):  
Zhengyi Cao ◽  
Yuning Cheng ◽  
Jiyin Wang ◽  
Yujuan Liu ◽  
Ruixiang Yang ◽  
...  

Abstract Background Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism of transcriptional regulation and singularly activation of AFP gene in hepatoma is not clear. Methods The expression of transcription factor HBP1 and AFP and clinical significance were further analyzed in hepatoma tissues from the patients who received surgery or TACE and then monitored for relapse for up 10 years. HBP1-mediated transcriptional regulation of AFP was analyzed by Western blotting, Luciferase assay, Realtime-PCR, ChIP and EMSA. After verified the axis of HBP-AFP, its impact on hepatoma was measured by MTT, Transwell and FACS in hepatoma cells and by tumorigenesis in HBP1−/− mice. Results The relative expressions of HBP1 and AFP correlated with survival and prognosis in hepatoma patients. HBP1 repressed the expression of AFP gene by directly binding to the AFP gene promoter. Hepatitis B Virus (HBV)-encoded protein HBx promoted malignancy in hepatoma cells through binding to HBP1 directly. Icaritin, an active ingredient of Chinese herb epimedium, inhibited malignancy in hepatoma cells through enhancing HBP1 transrepression of AFP. The repression of AFP by HBP1 attenuated AFP effect on PTEN, MMP9 and caspase-3, thus inhibited proliferation and migration, and induced apoptosis in hepatoma cells. The deregulation of AFP by HBP1 contributed to hepatoma progression in mice. Conclusions Our data clarify the mechanism of HBP1 in inhibiting the expression of AFP and its suppression in malignancy of hepatoma cells, providing a more comprehensive theoretical basis and potential solutions for the diagnosis and treatment of hepatoma.


2016 ◽  
Vol 397 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Nicola Groll ◽  
Ferdinand Kollotzek ◽  
Jens Goepfert ◽  
Thomas O. Joos ◽  
Michael Schwarz ◽  
...  

Abstract The antiepileptic drug phenobarbital (PB) exerts hepatic effects related to cell proliferation and tumorigenesis which are closely linked to the Wnt/β-catenin signaling pathway. This pathway is, amongst others, regulated by calpain proteases. We now identified PB as an inhibitor of Wnt/β-catenin signaling in mouse hepatoma cells. Further analyses revealed that PB inhibits calpain activity, an effect which is at least in parts mediated by a transcriptional regulation of calpain mRNA levels and which is furthermore independent of the constitutive androstane receptor, the known mediator of most effects of PB in liver cells.


1997 ◽  
Vol 328 (2) ◽  
pp. 393-399 ◽  
Author(s):  
B. Luis AGELLON ◽  
K. Sukhinder CHEEMA

To investigate the importance of the 3ʹ-untranslated region (UTR) of the mouse cholesterol 7α-hydroxylase (cyp7) mRNA in post-transcriptional regulation of expression of the cyp7 gene, chimaeric genes encoding mRNA containing the structural sequence of chloramphenicol acetyltransferase (CAT) linked to either the 3ʹ-UTR of the mouse cyp7 mRNA or the SV40 early gene mRNA were constructed. The human cytomegalovirus (CMV) promoter was used to drive the expression of all the chimaeric genes. Thus the transgenes had identical sequences in the promoter, the regions encoding the 5ʹ-UTR and translated sequence but differed in the region encoding the 3ʹ-UTR of their respective mRNA species. The transgene containing the entire cyp7 3ʹ-UTR (designated CMV.CAT.CYP7) gave rise to CAT activity in transfected hepatoma cells that was one-quarter of that obtained in cells transfected with the transgene containing the SV40 3ʹ-UTR (designated CMV.CAT.SV40). The 3ʹ-UTR of the cyp7 mRNA contains sequences resembling AU-rich elements (AREs). Deleting eight of nine putative AREs from the CYP7 3ʹ-UTR sequence increased the CAT activity to a level greater than that observed for CMV.CAT.SV40, whereas deletion of the intron region had no effect. These results show that the AREs of the 3ʹ-UTR of the cyp7 mRNA decrease transgene expression. Bile acids are known to repress the expression of the cyp7 gene. To test whether the 3ʹ-UTR of the cyp7 mRNA has a role in this process, the expression of the chimaeric genes was evaluated in hepatoma cells competent for bile acid uptake. Conjugated bile acids, but not unconjugated bile acids, further decreased the expression of the CMV.CAT.CYP7 transgene. The same bile acids had no effect on the expression of the CMV.CAT.SV40 transgene. Deletion of the intron from the cyp7 sequence did not alter the CAT activity compared with the parental plasmid, and also did not alter the sensitivity of the transgene to the conjugated bile acids. Deletion of the AREs from the cyp7 3ʹ-UTR, which increased the expression of the transgene, did not abolish the sensitivity of the transgene to repression by conjugated bile acids. Thus the 3ʹ-UTR of the mouse cyp7 mRNA also contains elements that facilitate the further repression of transgene expression in the presence of conjugated bile acids. The results indicate that the 3ʹ-UTR of the mouse cyp7 mRNA contains information specifying regulation at the post-transcriptional level.


2015 ◽  
Vol 85 ◽  
pp. 183-196 ◽  
Author(s):  
Alejandra Muñoz ◽  
Marcelo Villagrán ◽  
Paula Guzmán ◽  
Carlos Solíz ◽  
Marcell Gatica ◽  
...  

2020 ◽  
Author(s):  
Zhengyi Cao ◽  
Yuning Cheng ◽  
Jiyin Wang ◽  
Yujuan Liu ◽  
Ruixiang Yang ◽  
...  

Abstract Background: Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism of transcriptional regulation and singularly activation of AFP gene in hepatoma is not clear. Methods: The expression of transcription factor HBP1 and AFP and clinical significance were father analyzed in hepatoma tissues from the patients who received surgery or TACE and then monitored for relapse for up 10 years. HBP1-mediated transcriptional regulation of AFP was analyzed by Western blotting, luciferase assay, Realtime-PCR, ChIP and EMSA. After verified the axis of HBP-AFP, its impact on hepatoma was measured by MTT, Transwell and FACS in hepatoma cells and by tumorigenesis in HBP1-/- mice.Results: This study demonstrated that the relative expressions of HBP1 and AFP correlated with decreased survival and prognosis in hepatoma patients. HBP1 represses the expression of AFP gene by directly binding to the AFP gene promoter. Hepatitis B Virus (HBV)-encoded protein HBx promotes malignancy in hepatoma cells through binding to HBP1 directly. Icaritin, an active ingredient of Chinese herb epimedium, inhibits malignancy in hepatoma cells through enhancing HBP1 transrepression of AFP. The repression of AFP by HBP1 attenuates AFP effect on PTEN, MMP9 and caspase-3, thus inhibits proliferation and migration, and induces apoptosis in hepatoma cells. The deregulation of AFP by HBP1 contributes to hepatoma progression in mice. Conclusion: Our data clarify the mechanism of HBP1 in inhibiting the expression of AFP and its suppression in malignancy of hepatoma cells, providing a more comprehensive theoretical basis and potential solutions for the early diagnosis and treatment of hepatoma.


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