The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells

The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Medicine Wiley

The role of mmu‐miR‐155‐5p‐NF‐κB signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© 2018 Published by John Wiley & Sons Ltd.
ISSN
2045-7634
eISSN
2045-7634
D.O.I.
10.1002/cam4.1355
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Cancer MedicineWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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