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FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell

BACKGROUND: Although FOXO3a can inhibit the cell proliferation of prostate cancer, its relationship with reactive oxygen species (ROS) in prostate cancer (PCa) has not been reported. METHODS: We analyzed the correlation between the expression of FOXO3a and the antioxidant enzyme catalase in prostate...

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Autores principales: Tao, Yan, Liu, Shanhui, Lu, Jianzhong, Fu, Shengjun, Li, Lanlan, Zhang, Jing, Wang, Zhiping, Hong, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052560/
https://www.ncbi.nlm.nih.gov/pubmed/35488328
http://dx.doi.org/10.1186/s12894-022-01020-9
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author Tao, Yan
Liu, Shanhui
Lu, Jianzhong
Fu, Shengjun
Li, Lanlan
Zhang, Jing
Wang, Zhiping
Hong, Mei
author_facet Tao, Yan
Liu, Shanhui
Lu, Jianzhong
Fu, Shengjun
Li, Lanlan
Zhang, Jing
Wang, Zhiping
Hong, Mei
author_sort Tao, Yan
collection PubMed
description BACKGROUND: Although FOXO3a can inhibit the cell proliferation of prostate cancer, its relationship with reactive oxygen species (ROS) in prostate cancer (PCa) has not been reported. METHODS: We analyzed the correlation between the expression of FOXO3a and the antioxidant enzyme catalase in prostate cancer with the TCGA and GEPIA databases. We also constructed a PPI network of FOXO3a via the STRING database. The mRNA and protein expression of FOXO3a and catalase were detected by qRT-PCR or western blotting in LNCaP and 22RV1 cells treated with DHT, R1881, or Enzalutamide. The effects of FOXO3a on catalase expression were tested by over-expressing or knocking down FOXO3a in LNCaP cells. Furthermore, the catalase activity and ROS level were detected in LNCaP cells treated with DHT. Cell proliferation and ROS were also analyzed in LNCaP which was treated with antioxidant. RESULTS: Results showed that the catalase expression was down-regulated in prostate cancer. A positive correlation between FOXO3a and catalase existed. DHT treatment could significantly reduce FOXO3a and catalase expression at mRNA and protein level in LNCaP cells. Catalase expression partly depended on FOXO3a as over-expression and knockdown of FOXO3a could result in the expresssion change of catalase. DHT treatment was found to inhibit catalase activity and increase ROS level in prostate cancer cell. Our study also demonstrated that antioxidant treatment reduced DHT-induced proliferation and ROS production in prostate cancer cell. CONCLUSIONS: We discovered a novel mechanism by which DHT promotes prostate cancer cell proliferation via suppressing catalase activity and activating ROS signaling via a FOXO3a dependent manner. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-022-01020-9.
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spelling pubmed-90525602022-04-30 FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell Tao, Yan Liu, Shanhui Lu, Jianzhong Fu, Shengjun Li, Lanlan Zhang, Jing Wang, Zhiping Hong, Mei BMC Urol Research BACKGROUND: Although FOXO3a can inhibit the cell proliferation of prostate cancer, its relationship with reactive oxygen species (ROS) in prostate cancer (PCa) has not been reported. METHODS: We analyzed the correlation between the expression of FOXO3a and the antioxidant enzyme catalase in prostate cancer with the TCGA and GEPIA databases. We also constructed a PPI network of FOXO3a via the STRING database. The mRNA and protein expression of FOXO3a and catalase were detected by qRT-PCR or western blotting in LNCaP and 22RV1 cells treated with DHT, R1881, or Enzalutamide. The effects of FOXO3a on catalase expression were tested by over-expressing or knocking down FOXO3a in LNCaP cells. Furthermore, the catalase activity and ROS level were detected in LNCaP cells treated with DHT. Cell proliferation and ROS were also analyzed in LNCaP which was treated with antioxidant. RESULTS: Results showed that the catalase expression was down-regulated in prostate cancer. A positive correlation between FOXO3a and catalase existed. DHT treatment could significantly reduce FOXO3a and catalase expression at mRNA and protein level in LNCaP cells. Catalase expression partly depended on FOXO3a as over-expression and knockdown of FOXO3a could result in the expresssion change of catalase. DHT treatment was found to inhibit catalase activity and increase ROS level in prostate cancer cell. Our study also demonstrated that antioxidant treatment reduced DHT-induced proliferation and ROS production in prostate cancer cell. CONCLUSIONS: We discovered a novel mechanism by which DHT promotes prostate cancer cell proliferation via suppressing catalase activity and activating ROS signaling via a FOXO3a dependent manner. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-022-01020-9. BioMed Central 2022-04-29 /pmc/articles/PMC9052560/ /pubmed/35488328 http://dx.doi.org/10.1186/s12894-022-01020-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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
Tao, Yan
Liu, Shanhui
Lu, Jianzhong
Fu, Shengjun
Li, Lanlan
Zhang, Jing
Wang, Zhiping
Hong, Mei
FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell
title FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell
title_full FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell
title_fullStr FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell
title_full_unstemmed FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell
title_short FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell
title_sort foxo3a-ros pathway is involved in androgen-induced proliferation of prostate cancer cell
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052560/
https://www.ncbi.nlm.nih.gov/pubmed/35488328
http://dx.doi.org/10.1186/s12894-022-01020-9
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