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Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer
Oxaliplatin resistance is a challenge in the treatment of colorectal cancer (CRC) patients. Regulatory T cells (Tregs) are well known for their immunosuppressive roles, and targeting Tregs is an effective way to improve chemosensitivity. Exosome-delivered microRNA (miRNA) might be used as a potentia...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417448/ https://www.ncbi.nlm.nih.gov/pubmed/33905821 http://dx.doi.org/10.1016/j.ymthe.2021.04.028 |
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author | Ning, Tao Li, Jialu He, Yi Zhang, Haiyang Wang, Xinyi Deng, Ting Liu, Rui Li, Hongli Bai, Ming Fan, Qian Zhu, Kegan Ying, Guoguang Ba, Yi |
author_facet | Ning, Tao Li, Jialu He, Yi Zhang, Haiyang Wang, Xinyi Deng, Ting Liu, Rui Li, Hongli Bai, Ming Fan, Qian Zhu, Kegan Ying, Guoguang Ba, Yi |
author_sort | Ning, Tao |
collection | PubMed |
description | Oxaliplatin resistance is a challenge in the treatment of colorectal cancer (CRC) patients. Regulatory T cells (Tregs) are well known for their immunosuppressive roles, and targeting Tregs is an effective way to improve chemosensitivity. Exosome-delivered microRNA (miRNA) might be used as a potential biomarker for predicting chemosensitivity. However, the relationship between Tregs and exosomal miRNAs remains largely unknown. TaqMan low-density array was performed to screen the differentially expressed serum miRNAs from pooled serum of patients who had FOLFOX treatment. Differential expression was validated using qRT-PCR in individual samples. Exosomes were isolated by sequential differential centrifugation, and they were verified by transmission electron microscopy. The RNA and protein levels were determined by quantitative real-time PCR and western blotting. A mouse xenograft model was adopted to evaluate the correlation between exosome-derived miR-208b and Tregs in vivo. We demonstrated that circulating miR-208b is a non-invasive marker for predicting FOLFOX sensitivity in CRC. miR-208b in colon cancer was secreted by tumor cells in the pattern of exosomes, and oxaliplatin-resistant cells showed the most obvious phenomenon of miR-208b increase. Colon cancer cell-secreted miR-208b was sufficiently delivered into recipient T cells to promote Treg expansion by targeting programmed cell death factor 4 (PDCD4). Furthermore, in vivo studies indicated that Treg expansion mediated by cancer cell-secreted miR-208b resulted in tumor growth and oxaliplatin resistance. Our results demonstrate that tumor-secreted miR-208b promotes Treg expansion by targeting PDCD4, and it may be related to a decrease of oxaliplatin-based chemosensitivity in CRC. These findings highlight a potential role of exosomal miR-208b as a predictive biomarker for oxaliplatin-based therapy response, and they provide a novel target for immunotherapy. |
format | Online Article Text |
id | pubmed-8417448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-84174482022-09-01 Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer Ning, Tao Li, Jialu He, Yi Zhang, Haiyang Wang, Xinyi Deng, Ting Liu, Rui Li, Hongli Bai, Ming Fan, Qian Zhu, Kegan Ying, Guoguang Ba, Yi Mol Ther Original Article Oxaliplatin resistance is a challenge in the treatment of colorectal cancer (CRC) patients. Regulatory T cells (Tregs) are well known for their immunosuppressive roles, and targeting Tregs is an effective way to improve chemosensitivity. Exosome-delivered microRNA (miRNA) might be used as a potential biomarker for predicting chemosensitivity. However, the relationship between Tregs and exosomal miRNAs remains largely unknown. TaqMan low-density array was performed to screen the differentially expressed serum miRNAs from pooled serum of patients who had FOLFOX treatment. Differential expression was validated using qRT-PCR in individual samples. Exosomes were isolated by sequential differential centrifugation, and they were verified by transmission electron microscopy. The RNA and protein levels were determined by quantitative real-time PCR and western blotting. A mouse xenograft model was adopted to evaluate the correlation between exosome-derived miR-208b and Tregs in vivo. We demonstrated that circulating miR-208b is a non-invasive marker for predicting FOLFOX sensitivity in CRC. miR-208b in colon cancer was secreted by tumor cells in the pattern of exosomes, and oxaliplatin-resistant cells showed the most obvious phenomenon of miR-208b increase. Colon cancer cell-secreted miR-208b was sufficiently delivered into recipient T cells to promote Treg expansion by targeting programmed cell death factor 4 (PDCD4). Furthermore, in vivo studies indicated that Treg expansion mediated by cancer cell-secreted miR-208b resulted in tumor growth and oxaliplatin resistance. Our results demonstrate that tumor-secreted miR-208b promotes Treg expansion by targeting PDCD4, and it may be related to a decrease of oxaliplatin-based chemosensitivity in CRC. These findings highlight a potential role of exosomal miR-208b as a predictive biomarker for oxaliplatin-based therapy response, and they provide a novel target for immunotherapy. American Society of Gene & Cell Therapy 2021-09-01 2021-04-24 /pmc/articles/PMC8417448/ /pubmed/33905821 http://dx.doi.org/10.1016/j.ymthe.2021.04.028 Text en © 2021 The Author(s) 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 | Original Article Ning, Tao Li, Jialu He, Yi Zhang, Haiyang Wang, Xinyi Deng, Ting Liu, Rui Li, Hongli Bai, Ming Fan, Qian Zhu, Kegan Ying, Guoguang Ba, Yi Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer |
title | Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer |
title_full | Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer |
title_fullStr | Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer |
title_full_unstemmed | Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer |
title_short | Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer |
title_sort | exosomal mir-208b related with oxaliplatin resistance promotes treg expansion in colorectal cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417448/ https://www.ncbi.nlm.nih.gov/pubmed/33905821 http://dx.doi.org/10.1016/j.ymthe.2021.04.028 |
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