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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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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. |
format | Online Article Text |
id | pubmed-8015059 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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