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.
Cancer Medicine – Wiley
Published: Jan 1, 2018
Keywords: ; ; ; ;
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.
All for just $49/month
Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.
Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.
It’s easy to organize your research with our built-in tools.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera