Development of oral cancer therapy using exosome-derived miRNAs that regulate HBp17/FGFBP

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K10332
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Hiroshima University
• Principal Investigator: Shintani Tomoaki 広島大学, 病院(歯), 講師 (90403518)
• Co-Investigator(Kenkyū-buntansha): 岡本 哲治 東亜大学, その他の研究科, 教授 (00169153) ; 林堂 安貴 広島大学, 病院(歯), 講師 (70243251)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 微小環境 / 血管新生

Outline of Final Research Achievements

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. MiR-6887-5p was identified to have a predicted mRNA target matching the 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.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

我々は、ED-71がSCC/OSCC細胞のエクソソームmiR-6887-5pを刺激すること、そしてmiR-6887-5pがHBp17/FGFBP-1を直接標的とすることにより、in vitroおよびin vivoでの腫瘍増殖、SCC/OSCC細胞のコロニー形成を抑制することを報告した。我々の知見は、エクソソームmiR-6887-5pが、1α,25(OH)2D3およびそのアナログの高カルシウム血症効果を回避しつつ、HBp17/FGFBP-1を標的とするSCC腫瘍の治療薬となることを示唆している。