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Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression
Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) and Homeobox A5 (HOXA5) are both down-regulated in adrenocortical carcinoma (ACC), and HOXA5 is predicted to bind to the promoter of AKR1B10. We aimed to investigate whether HOXA5 could bind to AKR1B10 to regulate ACC cells proliferation and apoptosi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806264/ https://www.ncbi.nlm.nih.gov/pubmed/34027794 http://dx.doi.org/10.1080/21655979.2021.1924545 |
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author | Chen, Danyan Shen, Zhaonan Cheng, Xi Wang, Qi Zhou, Junlin Ren, Fang Sun, Yue Wang, Hongman Huang, Rongxi |
author_facet | Chen, Danyan Shen, Zhaonan Cheng, Xi Wang, Qi Zhou, Junlin Ren, Fang Sun, Yue Wang, Hongman Huang, Rongxi |
author_sort | Chen, Danyan |
collection | PubMed |
description | Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) and Homeobox A5 (HOXA5) are both down-regulated in adrenocortical carcinoma (ACC), and HOXA5 is predicted to bind to the promoter of AKR1B10. We aimed to investigate whether HOXA5 could bind to AKR1B10 to regulate ACC cells proliferation and apoptosis. The expression of AKR1B10 and HOXA5 in ACC patients and the relationship of their expression between ACC prognosis were evaluated by searching database. Then, NCI-H295R cells were overexpressed to detect the alteration of cell proliferation, apoptosis and the expression of p53 and p21 proteins. The interaction between AKR1B10 and HOXA5 was validated by luciferase report and chromatin immunoprecipitation. Finally, NCI-H295R cells were silenced with HOXA5 in the presence of AKR1B10 overexpression, and then cell proliferation and apoptosis were also assessed. Results revealed that AKR1B10 and HOXA5 are down-regulated in ACC patients and the low expression of it is correlated with low percent of overall survival (OS) and disease free survival (DFS). Compared with Y1 cells, SW-13 and NCI-H295R cells exerted lower expression of AKR1B10 and HOXA5. AKR1B10 significantly inhibited cell viability, colony formation and expression of Ki67 and PCNA, but promoted apoptosis and expression of p53 and p21 in NCI-H295R cells. HOXA5 could interact with AKR1B10 and enhance AKR1B10 expression. Furthermore, HOXA5 knockdown obviously blocked the effect of AKR1B10 overexpression on NCI-H295R cells proliferation and apoptosis. In conclusion, HOXA5 could bind to AKR1B10 promotor to increase its expression, activate p53 signaling, thereby inhibiting proliferation and promoting apoptosis of ACC cells. |
format | Online Article Text |
id | pubmed-8806264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-88062642022-02-02 Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression Chen, Danyan Shen, Zhaonan Cheng, Xi Wang, Qi Zhou, Junlin Ren, Fang Sun, Yue Wang, Hongman Huang, Rongxi Bioengineered Research Paper Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) and Homeobox A5 (HOXA5) are both down-regulated in adrenocortical carcinoma (ACC), and HOXA5 is predicted to bind to the promoter of AKR1B10. We aimed to investigate whether HOXA5 could bind to AKR1B10 to regulate ACC cells proliferation and apoptosis. The expression of AKR1B10 and HOXA5 in ACC patients and the relationship of their expression between ACC prognosis were evaluated by searching database. Then, NCI-H295R cells were overexpressed to detect the alteration of cell proliferation, apoptosis and the expression of p53 and p21 proteins. The interaction between AKR1B10 and HOXA5 was validated by luciferase report and chromatin immunoprecipitation. Finally, NCI-H295R cells were silenced with HOXA5 in the presence of AKR1B10 overexpression, and then cell proliferation and apoptosis were also assessed. Results revealed that AKR1B10 and HOXA5 are down-regulated in ACC patients and the low expression of it is correlated with low percent of overall survival (OS) and disease free survival (DFS). Compared with Y1 cells, SW-13 and NCI-H295R cells exerted lower expression of AKR1B10 and HOXA5. AKR1B10 significantly inhibited cell viability, colony formation and expression of Ki67 and PCNA, but promoted apoptosis and expression of p53 and p21 in NCI-H295R cells. HOXA5 could interact with AKR1B10 and enhance AKR1B10 expression. Furthermore, HOXA5 knockdown obviously blocked the effect of AKR1B10 overexpression on NCI-H295R cells proliferation and apoptosis. In conclusion, HOXA5 could bind to AKR1B10 promotor to increase its expression, activate p53 signaling, thereby inhibiting proliferation and promoting apoptosis of ACC cells. Taylor & Francis 2021-05-23 /pmc/articles/PMC8806264/ /pubmed/34027794 http://dx.doi.org/10.1080/21655979.2021.1924545 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Chen, Danyan Shen, Zhaonan Cheng, Xi Wang, Qi Zhou, Junlin Ren, Fang Sun, Yue Wang, Hongman Huang, Rongxi Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression |
title | Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression |
title_full | Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression |
title_fullStr | Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression |
title_full_unstemmed | Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression |
title_short | Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression |
title_sort | homeobox a5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing aldo-keto reductase family 1 member b10 expression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806264/ https://www.ncbi.nlm.nih.gov/pubmed/34027794 http://dx.doi.org/10.1080/21655979.2021.1924545 |
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