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HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression

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 o...

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Autores principales: Cao, Zhengyi, Cheng, Yuning, Wang, Jiyin, Liu, Yujuan, Yang, Ruixiang, Jiang, Wei, Li, Hui, Zhang, Xiaowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015059/
https://www.ncbi.nlm.nih.gov/pubmed/33794968
http://dx.doi.org/10.1186/s13046-021-01881-2
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author Cao, Zhengyi
Cheng, Yuning
Wang, Jiyin
Liu, Yujuan
Yang, Ruixiang
Jiang, Wei
Li, Hui
Zhang, Xiaowei
author_facet Cao, Zhengyi
Cheng, Yuning
Wang, Jiyin
Liu, Yujuan
Yang, Ruixiang
Jiang, Wei
Li, Hui
Zhang, Xiaowei
author_sort Cao, Zhengyi
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-01881-2.
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spelling pubmed-80150592021-04-01 HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression Cao, Zhengyi Cheng, Yuning Wang, Jiyin Liu, Yujuan Yang, Ruixiang Jiang, Wei Li, Hui Zhang, Xiaowei J Exp Clin Cancer Res Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-01881-2. BioMed Central 2021-04-01 /pmc/articles/PMC8015059/ /pubmed/33794968 http://dx.doi.org/10.1186/s13046-021-01881-2 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Cao, Zhengyi
Cheng, Yuning
Wang, Jiyin
Liu, Yujuan
Yang, Ruixiang
Jiang, Wei
Li, Hui
Zhang, Xiaowei
HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression
title HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression
title_full HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression
title_fullStr HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression
title_full_unstemmed HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression
title_short HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression
title_sort hbp1-mediated transcriptional repression of afp inhibits hepatoma progression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015059/
https://www.ncbi.nlm.nih.gov/pubmed/33794968
http://dx.doi.org/10.1186/s13046-021-01881-2
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