Eldecalcitol (ED-71)-induced exosomal miR-6887-5p suppresses squamous cell carcinoma cell growth by targeting heparin-binding protein 17/fibroblast growth factor–binding protein-1 (HBp17/FGFBP-1)

Higaki M.

Shintani T.

Hamada A.

Rosli S. N. Z.

Okamoto T.

In Vitro Cellular and Developmental Biology - Animal

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.

miR-6887-5p

Eldecalcitol (ED-71)

HBp17/FGFBP-1

Oral squamous cell carcinoma

Exosome

eng

The Society for In Vitro Biology

Springer Verlag

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。

[ISSN] 1071-2690

[ISSN] 1543-706X

[DOI] 10.1007/s11626-020-00440-x

[PMID] 32185608

[DOI] https://doi.org/10.1007/s11626-020-00440-x