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PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma
Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The bifunctional protein peroxiredoxin 6 (PRDX6), which has both calcium-independent phospholipase A2 (iPLA2) and glutathione peroxidase (GPx) activity, participates in the development of multiple tumors. However, the function and clinical...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547796/ https://www.ncbi.nlm.nih.gov/pubmed/36209344 http://dx.doi.org/10.1007/s12032-022-01822-9 |
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author | Li, Hong Wu, Zhengsheng Zhong, Rulei Zhang, Qikun Chen, Qixin Shen, Yuxian |
author_facet | Li, Hong Wu, Zhengsheng Zhong, Rulei Zhang, Qikun Chen, Qixin Shen, Yuxian |
author_sort | Li, Hong |
collection | PubMed |
description | Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The bifunctional protein peroxiredoxin 6 (PRDX6), which has both calcium-independent phospholipase A2 (iPLA2) and glutathione peroxidase (GPx) activity, participates in the development of multiple tumors. However, the function and clinical significance of PRDX6 in ICC remain unclear. In this study, we characterized PRDX6 in both human ICC and thioacetamide (TAA)-induced rat ICC. We found PRDX6 was significantly increased in ICC tissues, compared with the peritumoral tissues, and PRDX6 expression level was positively correlated with the malignant phenotype in ICC patients. Furthermore, PRDX6 genetic knockout significantly inhibited the tumor progression in rats. By using RNA sequencing analysis, we found 127 upregulated genes and 321 downregulated genes after PRDX6 knockout. In addition, we noticed a significant repression in the Wnt7a/b cascade, which has been shown to play an important role in the occurrence of ICC. We confirmed that gene expressions in the Wnt7a/b cascade were inhibited in ICC tissues after PRDX6 knockout by using qRT-PCR and immunohistochemistry analysis. Collectively, our findings suggest that PRDX6 may promote ICC by regulating the Wnt7a/b pathway, which could be a novel therapeutic target for ICC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12032-022-01822-9. |
format | Online Article Text |
id | pubmed-9547796 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-95477962022-10-10 PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma Li, Hong Wu, Zhengsheng Zhong, Rulei Zhang, Qikun Chen, Qixin Shen, Yuxian Med Oncol Original Paper Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The bifunctional protein peroxiredoxin 6 (PRDX6), which has both calcium-independent phospholipase A2 (iPLA2) and glutathione peroxidase (GPx) activity, participates in the development of multiple tumors. However, the function and clinical significance of PRDX6 in ICC remain unclear. In this study, we characterized PRDX6 in both human ICC and thioacetamide (TAA)-induced rat ICC. We found PRDX6 was significantly increased in ICC tissues, compared with the peritumoral tissues, and PRDX6 expression level was positively correlated with the malignant phenotype in ICC patients. Furthermore, PRDX6 genetic knockout significantly inhibited the tumor progression in rats. By using RNA sequencing analysis, we found 127 upregulated genes and 321 downregulated genes after PRDX6 knockout. In addition, we noticed a significant repression in the Wnt7a/b cascade, which has been shown to play an important role in the occurrence of ICC. We confirmed that gene expressions in the Wnt7a/b cascade were inhibited in ICC tissues after PRDX6 knockout by using qRT-PCR and immunohistochemistry analysis. Collectively, our findings suggest that PRDX6 may promote ICC by regulating the Wnt7a/b pathway, which could be a novel therapeutic target for ICC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12032-022-01822-9. Springer US 2022-10-08 2022 /pmc/articles/PMC9547796/ /pubmed/36209344 http://dx.doi.org/10.1007/s12032-022-01822-9 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/) . |
spellingShingle | Original Paper Li, Hong Wu, Zhengsheng Zhong, Rulei Zhang, Qikun Chen, Qixin Shen, Yuxian PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma |
title | PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma |
title_full | PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma |
title_fullStr | PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma |
title_full_unstemmed | PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma |
title_short | PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma |
title_sort | prdx6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547796/ https://www.ncbi.nlm.nih.gov/pubmed/36209344 http://dx.doi.org/10.1007/s12032-022-01822-9 |
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