Open AccessThe role of mmu‐miR‐155‐5p‐ NF ‐ κ B signaling in the education of bone marrow‐derived mesenchymal stem cells by gastric cancer cells
Author(s) -
Wang Mei,
Yang Fang,
Qiu Rong,
Zhu Mengchu,
Zhang Huiling,
Xu Wenrong,
Shen Bo,
Zhu Wei
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1355
Subject(s) - mesenchymal stem cell , nf κb , stromal cell , microbiology and biotechnology , bone marrow , chemistry , cancer research , progenitor cell , cancer cell , stem cell , biology , signal transduction , cancer , immunology , genetics
Bone marrow‐derived mesenchymal stem cells ( BM ‐ MSC s) are important precursors of tumor stromal cells. Previously, we have demonstrated that miR‐155‐5p inhibition directly induced transition of BM ‐ MSC s into gastric cancer‐associated MSC s. Whether miR‐155‐5p is involved in the education of BM ‐ MSC s by gastric cancer cells has not been established. Murine BM ‐ MSC s ( mMSC s) were isolated and grown in conditioned medium derived from gastric cancer cell line MFC ( MFC ‐ CM ). The tumor‐promoting phenotype and function of mMSC s were detected by immunofluorescence staining, quantitative reverse transcription‐polymerase chain reaction ( q RT ‐ 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 ‐ κ B) p65 and mmu‐miR‐155‐5p. mi RNA mimics, inhibitor, and the NF ‐ κ B inhibitor pyrrolidine dithiocarbamic acid ( PDTC ) were used to evaluate the role of miR‐155‐5p‐ NF ‐ κ B signaling in the education of mMSC s by MFC‐CM. We successfully established the education model of mMSC s by MFC ‐ CM and found that mmu‐miR‐155‐5p expression levels were reduced in mMSC s. Mimicking this deregulation by transfecting mi RNA inhibitor into mMSC s produced a similar effect as that of MFC ‐ CM on mMSC s. NF ‐ κ B p65 was validated as a target of mmu‐miR‐155‐5p, which also negatively regulated NF ‐ κ B activation. Inhibition of NF ‐ κ B activation by PDTC abolished the effect of the mi RNA inhibitor on mMSC s. mmu‐miR‐155‐5p overexpression partially blocked the effect of MFC ‐ CM in educating mMSC s, while PDTC treatment completely eliminated MFC ‐ CM activity. These results indicate that miR‐155‐5p is not the sole mi RNA mediating the education of BM ‐ MSC s by gastric cancer cells, but downstream NF ‐ κ B signaling is indispensable for this process.