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Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer
Background: Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511657/ https://www.ncbi.nlm.nih.gov/pubmed/31190980 http://dx.doi.org/10.2147/CMAR.S198886 |
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author | Ren, WeiHong Zhang, XuRan Li, WenBo Feng, Qian Feng, HuiJie Tong, Yan Rong, Hao Wang, Wei Zhang, Dai Zhang, ZhenQiang Tu, ShiChun Zhu, XiaoYan Zhang, QinXian |
author_facet | Ren, WeiHong Zhang, XuRan Li, WenBo Feng, Qian Feng, HuiJie Tong, Yan Rong, Hao Wang, Wei Zhang, Dai Zhang, ZhenQiang Tu, ShiChun Zhu, XiaoYan Zhang, QinXian |
author_sort | Ren, WeiHong |
collection | PubMed |
description | Background: Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the mechanisms of which are largely unknown. Methods: The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and ARG1, DICER1, PTEN, PI3K, AKT, mTOR, and NF-kB mRNAs were quantified by quantitative reverse tanscription PCR. Dual-Luciferase Reports Assay were used to examine the expression of genes which was targeted by miR-107. The expression of proteins were analyzed by using western blot. Results: MiR-107 was not only overexpressed in gastric cancer cells but also enriched in their secreted TDEs. Also, these miR-107 enriched TDEs could be taken up by HLA-DR(-)CD33(+)MDSCs, where miR-107 was able to target and suppress expression of DICER1 and PTEN genes. Dampened DICER1 expression supported expansion of MDSCs , while decreased PTEN led to activation of the PI3K pathway, resulting in increased ARG1 expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11b(+)Gr1(+/high )MDSCs in mouse peripheral blood and altering expression of DICER1, PTEN, ARG1, and NOS2 in the MDSCs. Conclusions: Our findings demonstrate for the first time that gastric cancer-secreted exosomes are able to deliver miR-107 to the host MDSCs where they induce their expansion and activition by targeting DICER1 and PTEN genes, thereby may provide novel cancer therapeutics target for gastric cancer. |
format | Online Article Text |
id | pubmed-6511657 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-65116572019-06-12 Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer Ren, WeiHong Zhang, XuRan Li, WenBo Feng, Qian Feng, HuiJie Tong, Yan Rong, Hao Wang, Wei Zhang, Dai Zhang, ZhenQiang Tu, ShiChun Zhu, XiaoYan Zhang, QinXian Cancer Manag Res Original Research Background: Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the mechanisms of which are largely unknown. Methods: The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and ARG1, DICER1, PTEN, PI3K, AKT, mTOR, and NF-kB mRNAs were quantified by quantitative reverse tanscription PCR. Dual-Luciferase Reports Assay were used to examine the expression of genes which was targeted by miR-107. The expression of proteins were analyzed by using western blot. Results: MiR-107 was not only overexpressed in gastric cancer cells but also enriched in their secreted TDEs. Also, these miR-107 enriched TDEs could be taken up by HLA-DR(-)CD33(+)MDSCs, where miR-107 was able to target and suppress expression of DICER1 and PTEN genes. Dampened DICER1 expression supported expansion of MDSCs , while decreased PTEN led to activation of the PI3K pathway, resulting in increased ARG1 expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11b(+)Gr1(+/high )MDSCs in mouse peripheral blood and altering expression of DICER1, PTEN, ARG1, and NOS2 in the MDSCs. Conclusions: Our findings demonstrate for the first time that gastric cancer-secreted exosomes are able to deliver miR-107 to the host MDSCs where they induce their expansion and activition by targeting DICER1 and PTEN genes, thereby may provide novel cancer therapeutics target for gastric cancer. Dove 2019-05-06 /pmc/articles/PMC6511657/ /pubmed/31190980 http://dx.doi.org/10.2147/CMAR.S198886 Text en © 2019 Ren et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Ren, WeiHong Zhang, XuRan Li, WenBo Feng, Qian Feng, HuiJie Tong, Yan Rong, Hao Wang, Wei Zhang, Dai Zhang, ZhenQiang Tu, ShiChun Zhu, XiaoYan Zhang, QinXian Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer |
title | Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer |
title_full | Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer |
title_fullStr | Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer |
title_full_unstemmed | Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer |
title_short | Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer |
title_sort | exosomal mirna-107 induces myeloid-derived suppressor cell expansion in gastric cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511657/ https://www.ncbi.nlm.nih.gov/pubmed/31190980 http://dx.doi.org/10.2147/CMAR.S198886 |
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