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Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer
BACKGROUND: Cancer stem cells are suggested to contribute to the extremely poor prognosis of pancreatic ductal adenocarcinoma and dysregulation of symmetric and asymmetric stem cell division may be involved. Anticancer benefits of phytochemicals like the polyphenol quercetin, present in many fruits,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282715/ https://www.ncbi.nlm.nih.gov/pubmed/28137273 http://dx.doi.org/10.1186/s12943-017-0589-8 |
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author | Nwaeburu, Clifford C. Abukiwan, Alia Zhao, Zhefu Herr, Ingrid |
author_facet | Nwaeburu, Clifford C. Abukiwan, Alia Zhao, Zhefu Herr, Ingrid |
author_sort | Nwaeburu, Clifford C. |
collection | PubMed |
description | BACKGROUND: Cancer stem cells are suggested to contribute to the extremely poor prognosis of pancreatic ductal adenocarcinoma and dysregulation of symmetric and asymmetric stem cell division may be involved. Anticancer benefits of phytochemicals like the polyphenol quercetin, present in many fruits, nuts and vegetables, could be expedited by microRNAs, which orchestrate cell-fate decisions and tissue homeostasis. The mechanisms regulating the division mode of cancer stem cells in relation to phytochemical-induced microRNAs are poorly understood. METHODS: Patient-derived pancreas tissue and 3 established pancreatic cancer cell lines were examined by immunofluorescence and time-lapse microscopy, microRNA microarray analysis, bioinformatics and computational analysis, qRT-PCR, Western blot analysis, self-renewal and differentiation assays. RESULTS: We show that symmetric and asymmetric division occurred in patient tissues and in vitro, whereas symmetric divisions were more extensive. By microarray analysis, bioinformatics prediction and qRT-PCR, we identified and validated quercetin-induced microRNAs involved in Notch signaling/cell-fate determination. Further computational analysis distinguished miR-200b-3p as strong candidate for cell-fate determinant. Mechanistically, miR-200b-3p switched symmetric to asymmetric cell division by reversing the Notch/Numb ratio, inhibition of the self-renewal and activation of the potential to differentiate to adipocytes, osteocytes and chondrocytes. Low miR-200b-3p levels fostered Notch signaling and promoted daughter cells to become symmetric while high miR-200b-3p levels lessened Notch signaling and promoted daughter cells to become asymmetric. CONCLUSIONS: Our findings provide a better understanding of the cross talk between phytochemicals, microRNAs and Notch signaling in the regulation of self-renewing cancer stem cell divisions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-017-0589-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5282715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-52827152017-02-03 Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer Nwaeburu, Clifford C. Abukiwan, Alia Zhao, Zhefu Herr, Ingrid Mol Cancer Research BACKGROUND: Cancer stem cells are suggested to contribute to the extremely poor prognosis of pancreatic ductal adenocarcinoma and dysregulation of symmetric and asymmetric stem cell division may be involved. Anticancer benefits of phytochemicals like the polyphenol quercetin, present in many fruits, nuts and vegetables, could be expedited by microRNAs, which orchestrate cell-fate decisions and tissue homeostasis. The mechanisms regulating the division mode of cancer stem cells in relation to phytochemical-induced microRNAs are poorly understood. METHODS: Patient-derived pancreas tissue and 3 established pancreatic cancer cell lines were examined by immunofluorescence and time-lapse microscopy, microRNA microarray analysis, bioinformatics and computational analysis, qRT-PCR, Western blot analysis, self-renewal and differentiation assays. RESULTS: We show that symmetric and asymmetric division occurred in patient tissues and in vitro, whereas symmetric divisions were more extensive. By microarray analysis, bioinformatics prediction and qRT-PCR, we identified and validated quercetin-induced microRNAs involved in Notch signaling/cell-fate determination. Further computational analysis distinguished miR-200b-3p as strong candidate for cell-fate determinant. Mechanistically, miR-200b-3p switched symmetric to asymmetric cell division by reversing the Notch/Numb ratio, inhibition of the self-renewal and activation of the potential to differentiate to adipocytes, osteocytes and chondrocytes. Low miR-200b-3p levels fostered Notch signaling and promoted daughter cells to become symmetric while high miR-200b-3p levels lessened Notch signaling and promoted daughter cells to become asymmetric. CONCLUSIONS: Our findings provide a better understanding of the cross talk between phytochemicals, microRNAs and Notch signaling in the regulation of self-renewing cancer stem cell divisions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-017-0589-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-01-31 /pmc/articles/PMC5282715/ /pubmed/28137273 http://dx.doi.org/10.1186/s12943-017-0589-8 Text en © The Author(s). 2017 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 Nwaeburu, Clifford C. Abukiwan, Alia Zhao, Zhefu Herr, Ingrid Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer |
title | Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer |
title_full | Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer |
title_fullStr | Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer |
title_full_unstemmed | Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer |
title_short | Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer |
title_sort | quercetin-induced mir-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282715/ https://www.ncbi.nlm.nih.gov/pubmed/28137273 http://dx.doi.org/10.1186/s12943-017-0589-8 |
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