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Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. However, the potential role and molecular mechani...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020597/ https://www.ncbi.nlm.nih.gov/pubmed/32082080 http://dx.doi.org/10.1186/s12935-020-1124-3 |
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author | Xiao, Zhiyuan Wei, Zhigang Deng, Danling Zheng, Zhe Zhao, Yali Jiang, Shenglu Zhang, Dan Zhang, Ling-Jie Fan, Mingmei Chen, Siqi Wang, ShuYang Ding, Yanqing Ye, Yaping Jiao, Hongli |
author_facet | Xiao, Zhiyuan Wei, Zhigang Deng, Danling Zheng, Zhe Zhao, Yali Jiang, Shenglu Zhang, Dan Zhang, Ling-Jie Fan, Mingmei Chen, Siqi Wang, ShuYang Ding, Yanqing Ye, Yaping Jiao, Hongli |
author_sort | Xiao, Zhiyuan |
collection | PubMed |
description | BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. However, the potential role and molecular mechanism of Siah1 in the development and progression of CRC is still unclear. METHODS: To explore the role and molecular mechanism of Siah1 in the development and progression of CRC, we examined the expression of Siah1 in CRC tissue samples and analyzed its association with progression and prognosis in CRC. In addition, overexpression and knockdown of Siah1 was used to investigate its activity in CRC cells. We also use bioinformatics to analyze and verify the significant roles of Siah1 in critical signaling pathways of CRC. RESULTS: We found that the expression of Siah1 was significantly downregulated in CRC tissues, and low expression of Siah1 was associated with aggressive TNM staging and poor survival of CRC patients. Moreover, we revealed that overexpression of Siah1 in CRC cells markedly inhibited CRC cell proliferation and invasion in vitro and in vivo, while knockdown of Siah1 enhanced CRC cell proliferation and invasion. Furthermore, we found that Siah1 prohibited cell proliferation and invasion in CRC partially through promoting AKT (the serine-threonine protein kinase) and YAP (yes associated protein) ubiquitylation and proteasome degradation to regulate the activity of MAPK(mitogen-activated protein kinase 1), PI3K-AKT (phosphatidylinositol 3-kinase-the serine-threonine protein kinase) and Hippo signaling pathways. CONCLUSIONS: These findings suggested that Siah1 is a novel potential prognostic biomarker and plays a tumor suppressor role in the development and progression of CRC. |
format | Online Article Text |
id | pubmed-7020597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-70205972020-02-20 Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation Xiao, Zhiyuan Wei, Zhigang Deng, Danling Zheng, Zhe Zhao, Yali Jiang, Shenglu Zhang, Dan Zhang, Ling-Jie Fan, Mingmei Chen, Siqi Wang, ShuYang Ding, Yanqing Ye, Yaping Jiao, Hongli Cancer Cell Int Primary Research BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. However, the potential role and molecular mechanism of Siah1 in the development and progression of CRC is still unclear. METHODS: To explore the role and molecular mechanism of Siah1 in the development and progression of CRC, we examined the expression of Siah1 in CRC tissue samples and analyzed its association with progression and prognosis in CRC. In addition, overexpression and knockdown of Siah1 was used to investigate its activity in CRC cells. We also use bioinformatics to analyze and verify the significant roles of Siah1 in critical signaling pathways of CRC. RESULTS: We found that the expression of Siah1 was significantly downregulated in CRC tissues, and low expression of Siah1 was associated with aggressive TNM staging and poor survival of CRC patients. Moreover, we revealed that overexpression of Siah1 in CRC cells markedly inhibited CRC cell proliferation and invasion in vitro and in vivo, while knockdown of Siah1 enhanced CRC cell proliferation and invasion. Furthermore, we found that Siah1 prohibited cell proliferation and invasion in CRC partially through promoting AKT (the serine-threonine protein kinase) and YAP (yes associated protein) ubiquitylation and proteasome degradation to regulate the activity of MAPK(mitogen-activated protein kinase 1), PI3K-AKT (phosphatidylinositol 3-kinase-the serine-threonine protein kinase) and Hippo signaling pathways. CONCLUSIONS: These findings suggested that Siah1 is a novel potential prognostic biomarker and plays a tumor suppressor role in the development and progression of CRC. BioMed Central 2020-02-13 /pmc/articles/PMC7020597/ /pubmed/32082080 http://dx.doi.org/10.1186/s12935-020-1124-3 Text en © The Author(s) 2020 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/. The Creative Commons Public Domain Dedication waiver (http://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 Xiao, Zhiyuan Wei, Zhigang Deng, Danling Zheng, Zhe Zhao, Yali Jiang, Shenglu Zhang, Dan Zhang, Ling-Jie Fan, Mingmei Chen, Siqi Wang, ShuYang Ding, Yanqing Ye, Yaping Jiao, Hongli Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation |
title | Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation |
title_full | Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation |
title_fullStr | Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation |
title_full_unstemmed | Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation |
title_short | Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation |
title_sort | downregulation of siah1 promotes colorectal cancer cell proliferation and migration by regulating akt and yap ubiquitylation and proteasome degradation |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020597/ https://www.ncbi.nlm.nih.gov/pubmed/32082080 http://dx.doi.org/10.1186/s12935-020-1124-3 |
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