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Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy
Tumor recurrence is often attributed to cancer stem cells (CSCs). We previously demonstrated that down-regulation of Pregnane X Receptor (PXR) decreases the chemoresistance of CSCs and prevents colorectal cancer recurrence. Currently, no PXR inhibitor is usable in clinic. Here, we identify miR-148a...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023769/ https://www.ncbi.nlm.nih.gov/pubmed/35276090 http://dx.doi.org/10.1016/j.stemcr.2022.02.005 |
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author | Bansard, Lucile Bouvet, Océane Moutin, Elisa Le Gall, Gaétan Giammona, Alessandro Pothin, Elodie Bacou, Marion Hassen-Khodja, Cédric Bordignon, Benoit Bourgaux, Jean François Prudhomme, Michel Hollande, Frédéric Pannequin, Julie Pascussi, Jean Marc Planque, Chris |
author_facet | Bansard, Lucile Bouvet, Océane Moutin, Elisa Le Gall, Gaétan Giammona, Alessandro Pothin, Elodie Bacou, Marion Hassen-Khodja, Cédric Bordignon, Benoit Bourgaux, Jean François Prudhomme, Michel Hollande, Frédéric Pannequin, Julie Pascussi, Jean Marc Planque, Chris |
author_sort | Bansard, Lucile |
collection | PubMed |
description | Tumor recurrence is often attributed to cancer stem cells (CSCs). We previously demonstrated that down-regulation of Pregnane X Receptor (PXR) decreases the chemoresistance of CSCs and prevents colorectal cancer recurrence. Currently, no PXR inhibitor is usable in clinic. Here, we identify miR-148a as a targetable element upstream of PXR signaling in CSCs, which when over-expressed decreases PXR expression and impairs tumor relapse after chemotherapy in mouse tumor xenografts. We then develop a fluorescent reporter screen for miR-148a activators and identify the anti-helminthic drug niclosamide as an inducer of miR-148a expression. Consequently, niclosamide decreased PXR expression and CSC numbers in colorectal cancer patient-derived cell lines and synergized with chemotherapeutic agents to prevent CSC chemoresistance and tumor recurrence in vivo. Our study suggests that endogenous miRNA inducers is a viable strategy to down-regulate PXR and illuminates niclosamide as a neoadjuvant repurposing strategy to prevent tumor relapse in colon cancer. |
format | Online Article Text |
id | pubmed-9023769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-90237692022-04-23 Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy Bansard, Lucile Bouvet, Océane Moutin, Elisa Le Gall, Gaétan Giammona, Alessandro Pothin, Elodie Bacou, Marion Hassen-Khodja, Cédric Bordignon, Benoit Bourgaux, Jean François Prudhomme, Michel Hollande, Frédéric Pannequin, Julie Pascussi, Jean Marc Planque, Chris Stem Cell Reports Article Tumor recurrence is often attributed to cancer stem cells (CSCs). We previously demonstrated that down-regulation of Pregnane X Receptor (PXR) decreases the chemoresistance of CSCs and prevents colorectal cancer recurrence. Currently, no PXR inhibitor is usable in clinic. Here, we identify miR-148a as a targetable element upstream of PXR signaling in CSCs, which when over-expressed decreases PXR expression and impairs tumor relapse after chemotherapy in mouse tumor xenografts. We then develop a fluorescent reporter screen for miR-148a activators and identify the anti-helminthic drug niclosamide as an inducer of miR-148a expression. Consequently, niclosamide decreased PXR expression and CSC numbers in colorectal cancer patient-derived cell lines and synergized with chemotherapeutic agents to prevent CSC chemoresistance and tumor recurrence in vivo. Our study suggests that endogenous miRNA inducers is a viable strategy to down-regulate PXR and illuminates niclosamide as a neoadjuvant repurposing strategy to prevent tumor relapse in colon cancer. Elsevier 2022-03-10 /pmc/articles/PMC9023769/ /pubmed/35276090 http://dx.doi.org/10.1016/j.stemcr.2022.02.005 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Bansard, Lucile Bouvet, Océane Moutin, Elisa Le Gall, Gaétan Giammona, Alessandro Pothin, Elodie Bacou, Marion Hassen-Khodja, Cédric Bordignon, Benoit Bourgaux, Jean François Prudhomme, Michel Hollande, Frédéric Pannequin, Julie Pascussi, Jean Marc Planque, Chris Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy |
title | Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy |
title_full | Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy |
title_fullStr | Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy |
title_full_unstemmed | Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy |
title_short | Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy |
title_sort | niclosamide induces mir-148a to inhibit pxr and sensitize colon cancer stem cells to chemotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023769/ https://www.ncbi.nlm.nih.gov/pubmed/35276090 http://dx.doi.org/10.1016/j.stemcr.2022.02.005 |
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