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Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation
BACKGROUND: A hypoxic microenvironment leads to an increase in the invasiveness and the metastatic potential of cancer cells within tumors via the epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. However, hypoxia-induced changes in the expression and function of candidate ste...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375212/ https://www.ncbi.nlm.nih.gov/pubmed/30760238 http://dx.doi.org/10.1186/s12885-019-5360-7 |
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author | Kang, Nahyeon Choi, Su Yeon Kim, Bit Na Yeo, Chang Dong Park, Chan Kwon Kim, Young Kyoon Kim, Tae-Jung Lee, Seong-Beom Lee, Sug Hyung Park, Jong Y. Park, Mi Sun Yim, Hyeon Woo Kim, Seung Joon |
author_facet | Kang, Nahyeon Choi, Su Yeon Kim, Bit Na Yeo, Chang Dong Park, Chan Kwon Kim, Young Kyoon Kim, Tae-Jung Lee, Seong-Beom Lee, Sug Hyung Park, Jong Y. Park, Mi Sun Yim, Hyeon Woo Kim, Seung Joon |
author_sort | Kang, Nahyeon |
collection | PubMed |
description | BACKGROUND: A hypoxic microenvironment leads to an increase in the invasiveness and the metastatic potential of cancer cells within tumors via the epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. However, hypoxia-induced changes in the expression and function of candidate stem cell markers and their possible molecular mechanism is still not understood. METHODS: Lung cell lines were analyzed in normoxic or hypoxic conditions. For screening among the stem cell markers, a transcriptome analysis using next-generation sequencing was performed. For validation, the EMT and stem cell characteristics were analyzed. To determine whether an epigenetic mechanism was involved, the cell lines were treated with a DNA methyltransferase inhibitor (AZA), and methylation-specific PCR and bisulfite sequencing were performed. RESULTS: Next-generation sequencing revealed that the CXCR4 expression was significantly higher after the hypoxic condition, which functionally resulted in the EMT and cancer stemness acquisition. The acquisition of the EMT and stemness properties was inhibited by treatment with CXCR4 siRNA. The CXCR4 was activated by either the hypoxic condition or treatment with AZA. The methylation-specific PCR and bisulfite sequencing displayed a decreased CXCR4 promoter methylation in the hypoxic condition. CONCLUSIONS: These results suggest that hypoxia-induced acquisition of cancer stem cell characteristics was associated with CXCR4 activation by its aberrant promoter demethylation. |
format | Online Article Text |
id | pubmed-6375212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63752122019-02-26 Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation Kang, Nahyeon Choi, Su Yeon Kim, Bit Na Yeo, Chang Dong Park, Chan Kwon Kim, Young Kyoon Kim, Tae-Jung Lee, Seong-Beom Lee, Sug Hyung Park, Jong Y. Park, Mi Sun Yim, Hyeon Woo Kim, Seung Joon BMC Cancer Research Article BACKGROUND: A hypoxic microenvironment leads to an increase in the invasiveness and the metastatic potential of cancer cells within tumors via the epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. However, hypoxia-induced changes in the expression and function of candidate stem cell markers and their possible molecular mechanism is still not understood. METHODS: Lung cell lines were analyzed in normoxic or hypoxic conditions. For screening among the stem cell markers, a transcriptome analysis using next-generation sequencing was performed. For validation, the EMT and stem cell characteristics were analyzed. To determine whether an epigenetic mechanism was involved, the cell lines were treated with a DNA methyltransferase inhibitor (AZA), and methylation-specific PCR and bisulfite sequencing were performed. RESULTS: Next-generation sequencing revealed that the CXCR4 expression was significantly higher after the hypoxic condition, which functionally resulted in the EMT and cancer stemness acquisition. The acquisition of the EMT and stemness properties was inhibited by treatment with CXCR4 siRNA. The CXCR4 was activated by either the hypoxic condition or treatment with AZA. The methylation-specific PCR and bisulfite sequencing displayed a decreased CXCR4 promoter methylation in the hypoxic condition. CONCLUSIONS: These results suggest that hypoxia-induced acquisition of cancer stem cell characteristics was associated with CXCR4 activation by its aberrant promoter demethylation. BioMed Central 2019-02-13 /pmc/articles/PMC6375212/ /pubmed/30760238 http://dx.doi.org/10.1186/s12885-019-5360-7 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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. |
spellingShingle | Research Article Kang, Nahyeon Choi, Su Yeon Kim, Bit Na Yeo, Chang Dong Park, Chan Kwon Kim, Young Kyoon Kim, Tae-Jung Lee, Seong-Beom Lee, Sug Hyung Park, Jong Y. Park, Mi Sun Yim, Hyeon Woo Kim, Seung Joon Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation |
title | Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation |
title_full | Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation |
title_fullStr | Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation |
title_full_unstemmed | Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation |
title_short | Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation |
title_sort | hypoxia-induced cancer stemness acquisition is associated with cxcr4 activation by its aberrant promoter demethylation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375212/ https://www.ncbi.nlm.nih.gov/pubmed/30760238 http://dx.doi.org/10.1186/s12885-019-5360-7 |
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