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Journal of Experimental & Clinical Cancer Research

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01-12-2021 | Hepatitis B | Research

HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression

Authors: Zhengyi Cao, Yuning Cheng, Jiyin Wang, Yujuan Liu, Ruixiang Yang, Wei Jiang, Hui Li, Xiaowei Zhang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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.

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Title: HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression
Authors: Zhengyi Cao
Yuning Cheng
Jiyin Wang
Yujuan Liu
Ruixiang Yang
Wei Jiang
Hui Li
Xiaowei Zhang
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Hepatitis B
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-01881-2

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Abstract

Background

Methods

Results

Conclusions

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