| RRC ID |
58820
|
| 著者 |
Higaki M, Shintani T, Hamada A, Rosli SNZ, Okamoto T.
|
| タイトル |
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).
|
| ジャーナル |
In Vitro Cell Dev Biol Anim
|
| 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.
|
| 巻・号 |
56(3)
|
| ページ |
222-233
|
| 公開日 |
2020-3-1
|
| DOI |
10.1007/s11626-020-00440-x
|
| PII |
10.1007/s11626-020-00440-x
|
| PMID |
32185608
|
| MeSH |
Animals
Base Sequence
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / pathology*
Cell Line, Tumor
Cell Proliferation / drug effects
Culture Media, Conditioned / pharmacology
Exosomes / drug effects
Exosomes / genetics*
Intercellular Signaling Peptides and Proteins / metabolism*
Male
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics*
MicroRNAs / metabolism
Mouth Neoplasms / genetics*
Mouth Neoplasms / pathology*
Up-Regulation / drug effects
Up-Regulation / genetics
Vitamin D / analogs & derivatives*
Vitamin D / pharmacology
|
| IF |
1.665
|
| 引用数 |
2
|
| リソース情報 |
| ヒト・動物細胞 |
A431
Ca9-22(RCB1976) |
