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Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival
OBJECTIVE: Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to invest...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400119/ https://www.ncbi.nlm.nih.gov/pubmed/30881116 http://dx.doi.org/10.2147/CMAR.S196485 |
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author | Chiang, Kun-Chun Huang, Sheng-Teng Wu, Ren-Chin Huang, Shih-Chiang Yeh, Ta-Sen Chen, Ming-Huang Hsu, Jun-Te Chen, Li-Wei Kuo, Sheng-Fong Chueh, Ho-Yen Juang, Horng-Heng Hung, Shuen-Iu Yeh, Chun-Nan Pang, Jong-Hwei S |
author_facet | Chiang, Kun-Chun Huang, Sheng-Teng Wu, Ren-Chin Huang, Shih-Chiang Yeh, Ta-Sen Chen, Ming-Huang Hsu, Jun-Te Chen, Li-Wei Kuo, Sheng-Fong Chueh, Ho-Yen Juang, Horng-Heng Hung, Shuen-Iu Yeh, Chun-Nan Pang, Jong-Hwei S |
author_sort | Chiang, Kun-Chun |
collection | PubMed |
description | OBJECTIVE: Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to investigate the role of IFI27 in CCA. MATERIALS AND METHODS: Cell proliferation, migration, and invasion assays, Western blot, gene transfection and knockdown, immunofluorescent and immunohistochemical stains, and xenograft animal model were applied. RESULTS: IFI27 knockdown in CCA cells induced cell cycle arrest in S phase, resulting in lower cell proliferative rate in vitro and in vivo. IFI27 knockdown attenuated CCA cell migration and invasion through inhibition of epithelial–mesenchymal transition, which was supported by increased E-cadherin and decreased N-cadherin and fibronectin. Filamentous actin level was also reduced. IFI27 knockdown further repressed expression and secretion of vascular endothelial growth factor (VEGF-A), a strong stimulator of angiogenesis, through downregulation of c-jun and c-fos, which was supported in vitro by the finding that human vascular endothelial cells grew more slowly in conditioned medium of IFI27 knockdown on CCA cells and in vivo by the lower erythropoietin concentration found in the xenografted tumors derived from IFI27 knockdown on CCA cells. In addition, anti-VEGF-A antibody treatment was able to repress CCA cell growth. To the contrary, IFI27 overexpression could increase CCA cell proliferation, migration, and invasion. Clinically, higher IFI27 expression was linked to inferior overall survival of CCA patients. CONCLUSION: Our data strongly suggest that IFI27 could be deemed as a potential target for CCA treatment. |
format | Online Article Text |
id | pubmed-6400119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64001192019-03-16 Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival Chiang, Kun-Chun Huang, Sheng-Teng Wu, Ren-Chin Huang, Shih-Chiang Yeh, Ta-Sen Chen, Ming-Huang Hsu, Jun-Te Chen, Li-Wei Kuo, Sheng-Fong Chueh, Ho-Yen Juang, Horng-Heng Hung, Shuen-Iu Yeh, Chun-Nan Pang, Jong-Hwei S Cancer Manag Res Original Research OBJECTIVE: Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to investigate the role of IFI27 in CCA. MATERIALS AND METHODS: Cell proliferation, migration, and invasion assays, Western blot, gene transfection and knockdown, immunofluorescent and immunohistochemical stains, and xenograft animal model were applied. RESULTS: IFI27 knockdown in CCA cells induced cell cycle arrest in S phase, resulting in lower cell proliferative rate in vitro and in vivo. IFI27 knockdown attenuated CCA cell migration and invasion through inhibition of epithelial–mesenchymal transition, which was supported by increased E-cadherin and decreased N-cadherin and fibronectin. Filamentous actin level was also reduced. IFI27 knockdown further repressed expression and secretion of vascular endothelial growth factor (VEGF-A), a strong stimulator of angiogenesis, through downregulation of c-jun and c-fos, which was supported in vitro by the finding that human vascular endothelial cells grew more slowly in conditioned medium of IFI27 knockdown on CCA cells and in vivo by the lower erythropoietin concentration found in the xenografted tumors derived from IFI27 knockdown on CCA cells. In addition, anti-VEGF-A antibody treatment was able to repress CCA cell growth. To the contrary, IFI27 overexpression could increase CCA cell proliferation, migration, and invasion. Clinically, higher IFI27 expression was linked to inferior overall survival of CCA patients. CONCLUSION: Our data strongly suggest that IFI27 could be deemed as a potential target for CCA treatment. Dove Medical Press 2019-02-28 /pmc/articles/PMC6400119/ /pubmed/30881116 http://dx.doi.org/10.2147/CMAR.S196485 Text en © 2019 Chiang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Chiang, Kun-Chun Huang, Sheng-Teng Wu, Ren-Chin Huang, Shih-Chiang Yeh, Ta-Sen Chen, Ming-Huang Hsu, Jun-Te Chen, Li-Wei Kuo, Sheng-Fong Chueh, Ho-Yen Juang, Horng-Heng Hung, Shuen-Iu Yeh, Chun-Nan Pang, Jong-Hwei S Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival |
title | Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival |
title_full | Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival |
title_fullStr | Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival |
title_full_unstemmed | Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival |
title_short | Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival |
title_sort | interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400119/ https://www.ncbi.nlm.nih.gov/pubmed/30881116 http://dx.doi.org/10.2147/CMAR.S196485 |
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