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Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p

BACKGROUND: Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are progenitor cells shown to migrate to the tumour and participate in the tumour microenvironment. BM-MSCs play important roles in tumour processes through the release of cytokines or exosomes; however, how BM-MSCs influence t...

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Detalles Bibliográficos
Autores principales: Li, Hongdan, Li, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173771/
https://www.ncbi.nlm.nih.gov/pubmed/30220706
http://dx.doi.org/10.1038/s41416-018-0254-z
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author Li, Hongdan
Li, Feng
author_facet Li, Hongdan
Li, Feng
author_sort Li, Hongdan
collection PubMed
description BACKGROUND: Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are progenitor cells shown to migrate to the tumour and participate in the tumour microenvironment. BM-MSCs play important roles in tumour processes through the release of cytokines or exosomes; however, how BM-MSCs influence the stemness of CSCs in colon cancer cells remains poorly understood. METHODS: We isolated exosomes from BM-MSCs and used these exosomes to treat colon cancer cells (HCT-116, HT-29 and SW-480). We compared stemness traits of colon CSCs by cell surface marker (CD133 and Lgr5) and functional assays, such as chemoresistance, colony formation, cell adhesion, invasion and tumour-formation assay. We performed a microRNA array to investigate the differences in exosomal microRNA expression between colon cancer cells, BM-MSCs and co-cultured cells and performed functional and molecular analysis of the gene targets. RESULTS: In this study, we found that BM-MSC-derived exosomes contained distinct microRNAs, including miR-142-3p, which in turn increased the population of CSCs in colon cancer cells. Depriving miR-142-3p from BM-MSC-derived exosomes clearly decreased the population of colon CSCs. Mechanistically, Numb was found to be the target gene of miR-142-3p, and miR-142-3p promoted the Notch signalling pathway by downregulating Numb. CONCLUSIONS: Our findings indicate that BM-MSC-derived exosomes promote colon cancer stem cell-like traits via miR-142-3p.
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spelling pubmed-61737712019-09-17 Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p Li, Hongdan Li, Feng Br J Cancer Article BACKGROUND: Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are progenitor cells shown to migrate to the tumour and participate in the tumour microenvironment. BM-MSCs play important roles in tumour processes through the release of cytokines or exosomes; however, how BM-MSCs influence the stemness of CSCs in colon cancer cells remains poorly understood. METHODS: We isolated exosomes from BM-MSCs and used these exosomes to treat colon cancer cells (HCT-116, HT-29 and SW-480). We compared stemness traits of colon CSCs by cell surface marker (CD133 and Lgr5) and functional assays, such as chemoresistance, colony formation, cell adhesion, invasion and tumour-formation assay. We performed a microRNA array to investigate the differences in exosomal microRNA expression between colon cancer cells, BM-MSCs and co-cultured cells and performed functional and molecular analysis of the gene targets. RESULTS: In this study, we found that BM-MSC-derived exosomes contained distinct microRNAs, including miR-142-3p, which in turn increased the population of CSCs in colon cancer cells. Depriving miR-142-3p from BM-MSC-derived exosomes clearly decreased the population of colon CSCs. Mechanistically, Numb was found to be the target gene of miR-142-3p, and miR-142-3p promoted the Notch signalling pathway by downregulating Numb. CONCLUSIONS: Our findings indicate that BM-MSC-derived exosomes promote colon cancer stem cell-like traits via miR-142-3p. Nature Publishing Group UK 2018-09-17 2018-09-11 /pmc/articles/PMC6173771/ /pubmed/30220706 http://dx.doi.org/10.1038/s41416-018-0254-z Text en © Cancer Research UK 2018 https://creativecommons.org/licenses/by/4.0/ This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Li, Hongdan
Li, Feng
Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p
title Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p
title_full Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p
title_fullStr Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p
title_full_unstemmed Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p
title_short Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p
title_sort exosomes from bm-mscs increase the population of cscs via transfer of mir-142-3p
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173771/
https://www.ncbi.nlm.nih.gov/pubmed/30220706
http://dx.doi.org/10.1038/s41416-018-0254-z
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