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The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells
Bone marrow‐derived mesenchymal stem cells (BM‐MSCs) are important precursors of tumor stromal cells. Previously, we have demonstrated that miR‐155‐5p inhibition directly induced transition of BM‐MSCs into gastric cancer‐associated MSCs. Whether miR‐155‐5p is involved in the education of BM‐MSCs by...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852371/ https://www.ncbi.nlm.nih.gov/pubmed/29441735 http://dx.doi.org/10.1002/cam4.1355 |
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author | Wang, Mei Yang, Fang Qiu, Rong Zhu, Mengchu Zhang, Huiling Xu, Wenrong Shen, Bo Zhu, Wei |
author_facet | Wang, Mei Yang, Fang Qiu, Rong Zhu, Mengchu Zhang, Huiling Xu, Wenrong Shen, Bo Zhu, Wei |
author_sort | Wang, Mei |
collection | PubMed |
description | Bone marrow‐derived mesenchymal stem cells (BM‐MSCs) are important precursors of tumor stromal cells. Previously, we have demonstrated that miR‐155‐5p inhibition directly induced transition of BM‐MSCs into gastric cancer‐associated MSCs. Whether miR‐155‐5p is involved in the education of BM‐MSCs by gastric cancer cells has not been established. Murine BM‐MSCs (mMSCs) were isolated and grown in conditioned medium derived from gastric cancer cell line MFC (MFC‐CM). The tumor‐promoting phenotype and function of mMSCs were detected by immunofluorescence staining, quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), cell colony formation assay, transwell migration, and invasion assays. Luciferase reporter assays and western blot analyses were conducted to reveal the relationship between nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) p65 and mmu‐miR‐155‐5p. miRNA mimics, inhibitor, and the NF‐κB inhibitor pyrrolidine dithiocarbamic acid (PDTC) were used to evaluate the role of miR‐155‐5p‐NF‐κB signaling in the education of mMSCs by MFC‐CM. We successfully established the education model of mMSCs by MFC‐CM and found that mmu‐miR‐155‐5p expression levels were reduced in mMSCs. Mimicking this deregulation by transfecting miRNA inhibitor into mMSCs produced a similar effect as that of MFC‐CM on mMSCs. NF‐κB p65 was validated as a target of mmu‐miR‐155‐5p, which also negatively regulated NF‐κB activation. Inhibition of NF‐κB activation by PDTC abolished the effect of the miRNA inhibitor on mMSCs. mmu‐miR‐155‐5p overexpression partially blocked the effect of MFC‐CM in educating mMSCs, while PDTC treatment completely eliminated MFC‐CM activity. These results indicate that miR‐155‐5p is not the sole miRNA mediating the education of BM‐MSCs by gastric cancer cells, but downstream NF‐κB signaling is indispensable for this process. |
format | Online Article Text |
id | pubmed-5852371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58523712018-03-22 The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells Wang, Mei Yang, Fang Qiu, Rong Zhu, Mengchu Zhang, Huiling Xu, Wenrong Shen, Bo Zhu, Wei Cancer Med Cancer Biology Bone marrow‐derived mesenchymal stem cells (BM‐MSCs) are important precursors of tumor stromal cells. Previously, we have demonstrated that miR‐155‐5p inhibition directly induced transition of BM‐MSCs into gastric cancer‐associated MSCs. Whether miR‐155‐5p is involved in the education of BM‐MSCs by gastric cancer cells has not been established. Murine BM‐MSCs (mMSCs) were isolated and grown in conditioned medium derived from gastric cancer cell line MFC (MFC‐CM). The tumor‐promoting phenotype and function of mMSCs were detected by immunofluorescence staining, quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), cell colony formation assay, transwell migration, and invasion assays. Luciferase reporter assays and western blot analyses were conducted to reveal the relationship between nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) p65 and mmu‐miR‐155‐5p. miRNA mimics, inhibitor, and the NF‐κB inhibitor pyrrolidine dithiocarbamic acid (PDTC) were used to evaluate the role of miR‐155‐5p‐NF‐κB signaling in the education of mMSCs by MFC‐CM. We successfully established the education model of mMSCs by MFC‐CM and found that mmu‐miR‐155‐5p expression levels were reduced in mMSCs. Mimicking this deregulation by transfecting miRNA inhibitor into mMSCs produced a similar effect as that of MFC‐CM on mMSCs. NF‐κB p65 was validated as a target of mmu‐miR‐155‐5p, which also negatively regulated NF‐κB activation. Inhibition of NF‐κB activation by PDTC abolished the effect of the miRNA inhibitor on mMSCs. mmu‐miR‐155‐5p overexpression partially blocked the effect of MFC‐CM in educating mMSCs, while PDTC treatment completely eliminated MFC‐CM activity. These results indicate that miR‐155‐5p is not the sole miRNA mediating the education of BM‐MSCs by gastric cancer cells, but downstream NF‐κB signaling is indispensable for this process. John Wiley and Sons Inc. 2018-02-14 /pmc/articles/PMC5852371/ /pubmed/29441735 http://dx.doi.org/10.1002/cam4.1355 Text en © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Wang, Mei Yang, Fang Qiu, Rong Zhu, Mengchu Zhang, Huiling Xu, Wenrong Shen, Bo Zhu, Wei The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells |
title | The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells |
title_full | The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells |
title_fullStr | The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells |
title_full_unstemmed | The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells |
title_short | The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells |
title_sort | role of mmu‐mir‐155‐5p‐nf‐κb signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852371/ https://www.ncbi.nlm.nih.gov/pubmed/29441735 http://dx.doi.org/10.1002/cam4.1355 |
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