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Integrative analysis the characterization of peroxiredoxins in pan-cancer
BACKGROUND: Peroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth. In addition, previous studies report that PRDXs play critical roles in the occurrence and development of carcinomas. However, few studies have c...
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/PMC8272277/ https://www.ncbi.nlm.nih.gov/pubmed/34246267 http://dx.doi.org/10.1186/s12935-021-02064-x |
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author | Gao, Lei Meng, Jialin Yue, Chuang Wu, Xingyu Su, Quanxin Wu, Hao Zhang, Ze Yu, Qinzhou Gao, Shenglin Fan, Song Zuo, Li |
author_facet | Gao, Lei Meng, Jialin Yue, Chuang Wu, Xingyu Su, Quanxin Wu, Hao Zhang, Ze Yu, Qinzhou Gao, Shenglin Fan, Song Zuo, Li |
author_sort | Gao, Lei |
collection | PubMed |
description | BACKGROUND: Peroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth. In addition, previous studies report that PRDXs play critical roles in the occurrence and development of carcinomas. However, few studies have conducted systematic analysis of PRDXs in cancers. Therefore, the present study sought to explore the molecular characteristics and potential clinical significance of PRDX family members in pan cancer and further validate the function of PRDX6 in bladder urothelial carcinoma (BLCA). METHODS: A comprehensive analysis of PRDXs in 33 types of cancer was performed based on the TCGA database. This involved an analysis of mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, both the gain and loss of function strategies were used to assess the importance and mechanism of PRDX6 in the cell cycle of BLCA. RESULT: Analysis showed abnormal expression of PRDX1-6 in several types of cancer compared to normal tissues. Univariate Cox proportional hazard regression analysis showed that expression levels of PRDX1, PRDX4 and PRDX6 were mostly associated with poor survival of OS, DSS and PFI, and PRDX2 and PRDX3 with favorable survival. In addition, the expression of PRDX genes were positively correlated with CNV and negatively with methylation. Moreover, analysis based on PharmacoDB dataset showed that the augmented levels of PRDX1, PRDX3 and PRDX6 were significantly correlated with EGFR/VEGFR inhibitor drugs. Furthermore, knocking down of PRDX6 inhibited growth of cancer cells through the JAK2-STAT3 in bladder cell lines. CONCLUSIONS: PRDXs are potential biomarkers and therapeutic targets for several carcinomas, especially for BLCA. In addition, PRDX6 could regulate proliferation of cancer cell via JAK2-STAT3 pathway and involve into the process of cell cycle in BLCA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02064-x. |
format | Online Article Text |
id | pubmed-8272277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-82722772021-07-12 Integrative analysis the characterization of peroxiredoxins in pan-cancer Gao, Lei Meng, Jialin Yue, Chuang Wu, Xingyu Su, Quanxin Wu, Hao Zhang, Ze Yu, Qinzhou Gao, Shenglin Fan, Song Zuo, Li Cancer Cell Int Primary Research BACKGROUND: Peroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth. In addition, previous studies report that PRDXs play critical roles in the occurrence and development of carcinomas. However, few studies have conducted systematic analysis of PRDXs in cancers. Therefore, the present study sought to explore the molecular characteristics and potential clinical significance of PRDX family members in pan cancer and further validate the function of PRDX6 in bladder urothelial carcinoma (BLCA). METHODS: A comprehensive analysis of PRDXs in 33 types of cancer was performed based on the TCGA database. This involved an analysis of mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, both the gain and loss of function strategies were used to assess the importance and mechanism of PRDX6 in the cell cycle of BLCA. RESULT: Analysis showed abnormal expression of PRDX1-6 in several types of cancer compared to normal tissues. Univariate Cox proportional hazard regression analysis showed that expression levels of PRDX1, PRDX4 and PRDX6 were mostly associated with poor survival of OS, DSS and PFI, and PRDX2 and PRDX3 with favorable survival. In addition, the expression of PRDX genes were positively correlated with CNV and negatively with methylation. Moreover, analysis based on PharmacoDB dataset showed that the augmented levels of PRDX1, PRDX3 and PRDX6 were significantly correlated with EGFR/VEGFR inhibitor drugs. Furthermore, knocking down of PRDX6 inhibited growth of cancer cells through the JAK2-STAT3 in bladder cell lines. CONCLUSIONS: PRDXs are potential biomarkers and therapeutic targets for several carcinomas, especially for BLCA. In addition, PRDX6 could regulate proliferation of cancer cell via JAK2-STAT3 pathway and involve into the process of cell cycle in BLCA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02064-x. BioMed Central 2021-07-10 /pmc/articles/PMC8272277/ /pubmed/34246267 http://dx.doi.org/10.1186/s12935-021-02064-x Text en © The Author(s) 2021 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 | Primary Research Gao, Lei Meng, Jialin Yue, Chuang Wu, Xingyu Su, Quanxin Wu, Hao Zhang, Ze Yu, Qinzhou Gao, Shenglin Fan, Song Zuo, Li Integrative analysis the characterization of peroxiredoxins in pan-cancer |
title | Integrative analysis the characterization of peroxiredoxins in pan-cancer |
title_full | Integrative analysis the characterization of peroxiredoxins in pan-cancer |
title_fullStr | Integrative analysis the characterization of peroxiredoxins in pan-cancer |
title_full_unstemmed | Integrative analysis the characterization of peroxiredoxins in pan-cancer |
title_short | Integrative analysis the characterization of peroxiredoxins in pan-cancer |
title_sort | integrative analysis the characterization of peroxiredoxins in pan-cancer |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272277/ https://www.ncbi.nlm.nih.gov/pubmed/34246267 http://dx.doi.org/10.1186/s12935-021-02064-x |
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