Development of the novel oral cancer therapy using molecular targeted nucleic acid medicine for Arl4c

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11501
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Kyushu University
• Principal Investigator: Fujii Shinsuke 九州大学, 歯学研究院, 助教 (60452786)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Arl4c / 扁平上皮癌 / 増殖 / DNAメチル化 / 増殖因子シグナル

Outline of Final Research Achievements

In this study, it was shown that the expression of ADP-ribosylation factor (ARF)-like 4c (Arl4c) in lung and tongue squamous cell carcinoma (SCC), its expression mechanism and its effect on SCC tumorigenesis.
Immunohistochemical analysis showed that Arl4c was not observed in non-tumor regions, but was overexpressed in tumor lesions in 70 ~ 80% of lung and tongue SCC. Knockout of Arl4c expression in NCI-H520 lung SCC cells and SAS tongue SCC cells reduced proliferation and migration capabilities in vitro. Arl4c expression was depended on MEK/MAP kinase signaling, but not on Wnt/β-catenin in SAS cells. Although inhibition of Wnt/β-catenin or MEK/MAP kinase signaling did not decrease Arl4c expression in NCI-H520 cells, Arl4c DNA was clearly hypomethylated in the 3’-untranslated region (UTR), leading to increase of Arl4c expression.

Free Research Field

口腔病理

Academic Significance and Societal Importance of the Research Achievements

扁平上皮癌は悪性度が高いことが知られているが、他の癌腫に認められるような遺伝子変異の報告がこれまで報告されていない。そのため新たな癌マーカーおよび治療標的となる因子の同定が待望されている。本研究の成果は、Arl4cがヒト扁平上皮癌において増殖因子シグナルに加えてDNAのメチル化により発現制御されていること、また、扁平上皮癌における新規診断マーカーや治療の標的になる可能性を示している。