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ID 51080
file
creator
Higaki, M.
Rosli, S. N. Z.
subject
miR-6887-5p
Eldecalcitol (ED-71)
HBp17/FGFBP-1
Oral squamous cell carcinoma
Exosome
abstract
Heparin-binding protein 17/fibroblast growth factor–binding protein-1 (HBp17/FGFBP-1) was purified from A431 cell-conditioned media based on its capacity to bind to fibroblast growth factor 1 and 2 (FGF-1 and FGF-2). HBp17/FGFBP-1 has been observed to induce the tumorigenic potential of epithelial cells and is highly expressed in oral cancer cell lines and tissues. HBp17/FGFBP-1 is also recognized as a pro-angiogenic molecule as a consequence of its interaction with FGF-2. We have previously reported that Eldecalcitol (ED-71), an analog of 1α,25(OH)2D3, downregulated the expression of HBp17/FGFBP-1 and inhibited the proliferation of squamous cell carcinoma (SCC) cells in vitro and in vivo through NF-κb inhibition. To explore the possibility of microRNA (miRNA) control of HBp17/FGFBP-1, we analyzed exosomal miRNAs from medium conditioned by A431 cells treated with ED-71. Microarray analysis revealed that 12 exosomal miRNAs were upregulated in ED-71-treated A431 cells. Among them, miR-6887-5p was identified to have a predicted mRNA target matching the 3′ untranslated region (3′-UTR) of HBp17/FGFBP-1. The 3′-UTR of HBp17/FGFBP-1 was confirmed to be a direct target of miR-6887-5p in SCC/OSCC cells, as assessed with a luciferase reporter assay. Functional assessment revealed that overexpression of miR-6887-5p in SCC/OSCC cells inhibited cell proliferation and colony formation in vitro, and inhibited tumor growth in vivo compared with control. In conclusion, our present study supports a novel anti-cancer mechanism involving the regulation of HBp17/FGFBP-1 function by exosomal miR-6887-5p in SCC/OSCC cells, which has potential utility as a miRNA-based cancer therapy.
description
This research was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology to T.O. (grant number: 15H05043) and T. S. (grant number: 16K11723).
journal title
In Vitro Cellular and Developmental Biology - Animal
volume
Volume 56
issue
Issue 3
start page
222
end page
233
date of issued
2020-03-17
publisher
The Society for In Vitro Biology
Springer Verlag
issn
1071-2690
1543-706X
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
This is a post-peer-review, pre-copyedit version of an article published in In Vitro Cellular and Developmental Biology - Animal. The final authenticated version is available online at: https://doi.org/10.1007/s11626-020-00440-x
This is not the published version. Please cite only the published version. この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。
relation url
department
University Medical Hospital
Graduate School of Biomedical & Health Sciences