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HMGB1 promotes the development of castration-resistant prostate cancer by regulating androgen receptor activation
AR signalling pathway reactivation plays a key role in the development of castration-resistant prostate cancer (CRPC). High-mobility group protein B1 (HMGB1) is an important factor involved in the occurrence and development of a variety of tumours by regulating gene transcription. In the present stu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535630/ https://www.ncbi.nlm.nih.gov/pubmed/36129149 http://dx.doi.org/10.3892/or.2022.8412 |
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author | Chen, Junyu Xu, Duo Wang, Taiwei Yang, Zhaoyun Yang, Yanrong He, Kang Zhao, Lijing |
author_facet | Chen, Junyu Xu, Duo Wang, Taiwei Yang, Zhaoyun Yang, Yanrong He, Kang Zhao, Lijing |
author_sort | Chen, Junyu |
collection | PubMed |
description | AR signalling pathway reactivation plays a key role in the development of castration-resistant prostate cancer (CRPC). High-mobility group protein B1 (HMGB1) is an important factor involved in the occurrence and development of a variety of tumours by regulating gene transcription. In the present study, the association between HMGB1 and prostate cancer (PCa) and the effects of HMGB1 on androgen receptor (AR) transcription and signalling pathway reactivation in PCa cells in vitro and in vivo were evaluated. A bioinformatics method was used to determine the mRNA expression level of HMGB1 in PCa specimens and its correlation with the mRNA expression of AR. Immunohistochemical staining was used to detect the expression of these proteins in clinical PCa samples. Reporter gene and ChIP assays were performed to determine the activity of AR and the effect of HMGB1 on the ability of AR to bind to the promoters of prostate specific antigen and transmembrane protease, serine 2. A bioluminescence resonance energy transfer assay was employed to observe the direct interaction between HMGB1 and AR protein. Additionally, a castrated nude mouse xenograft tumour model was established to verify the effect of HMGB1 on PCa. The results revealed that HMGB1 expression was significantly increased in PCa specimens, which may have a strong correlation with AR expression. Moreover, HMGB1 could reactivate the AR signalling pathway, directly interact with AR, and promote the development of CRPC in an androgen-independent manner. The results of the present study indicated that HMGB1 promoted the development of CRPC by interacting with AR, which inferred that decreasing the expression of HMGB1 may be a potential effective method for CRPC prevention and treatment. |
format | Online Article Text |
id | pubmed-9535630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-95356302022-10-21 HMGB1 promotes the development of castration-resistant prostate cancer by regulating androgen receptor activation Chen, Junyu Xu, Duo Wang, Taiwei Yang, Zhaoyun Yang, Yanrong He, Kang Zhao, Lijing Oncol Rep Articles AR signalling pathway reactivation plays a key role in the development of castration-resistant prostate cancer (CRPC). High-mobility group protein B1 (HMGB1) is an important factor involved in the occurrence and development of a variety of tumours by regulating gene transcription. In the present study, the association between HMGB1 and prostate cancer (PCa) and the effects of HMGB1 on androgen receptor (AR) transcription and signalling pathway reactivation in PCa cells in vitro and in vivo were evaluated. A bioinformatics method was used to determine the mRNA expression level of HMGB1 in PCa specimens and its correlation with the mRNA expression of AR. Immunohistochemical staining was used to detect the expression of these proteins in clinical PCa samples. Reporter gene and ChIP assays were performed to determine the activity of AR and the effect of HMGB1 on the ability of AR to bind to the promoters of prostate specific antigen and transmembrane protease, serine 2. A bioluminescence resonance energy transfer assay was employed to observe the direct interaction between HMGB1 and AR protein. Additionally, a castrated nude mouse xenograft tumour model was established to verify the effect of HMGB1 on PCa. The results revealed that HMGB1 expression was significantly increased in PCa specimens, which may have a strong correlation with AR expression. Moreover, HMGB1 could reactivate the AR signalling pathway, directly interact with AR, and promote the development of CRPC in an androgen-independent manner. The results of the present study indicated that HMGB1 promoted the development of CRPC by interacting with AR, which inferred that decreasing the expression of HMGB1 may be a potential effective method for CRPC prevention and treatment. D.A. Spandidos 2022-09-19 /pmc/articles/PMC9535630/ /pubmed/36129149 http://dx.doi.org/10.3892/or.2022.8412 Text en Copyright: © Chen et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Chen, Junyu Xu, Duo Wang, Taiwei Yang, Zhaoyun Yang, Yanrong He, Kang Zhao, Lijing HMGB1 promotes the development of castration-resistant prostate cancer by regulating androgen receptor activation |
title | HMGB1 promotes the development of castration-resistant prostate cancer by regulating androgen receptor activation |
title_full | HMGB1 promotes the development of castration-resistant prostate cancer by regulating androgen receptor activation |
title_fullStr | HMGB1 promotes the development of castration-resistant prostate cancer by regulating androgen receptor activation |
title_full_unstemmed | HMGB1 promotes the development of castration-resistant prostate cancer by regulating androgen receptor activation |
title_short | HMGB1 promotes the development of castration-resistant prostate cancer by regulating androgen receptor activation |
title_sort | hmgb1 promotes the development of castration-resistant prostate cancer by regulating androgen receptor activation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535630/ https://www.ncbi.nlm.nih.gov/pubmed/36129149 http://dx.doi.org/10.3892/or.2022.8412 |
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