Development of novel diagnosis and therapy based on exosome for oral carcinoma

• Project/Area Number: 17K17295
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Nihon University
• Principal Investigator: SHINOZUKA Keiji 日本大学, 歯学部, 助教 (30431745)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 口腔癌 / microRNA / ネットワーク解析 / microRNAアレイ解析 / 癌関連遺伝子 / エクソソーム / マイクロアレイ解析 / 口腔がん

Outline of Final Research Achievements

We performed microRNA microarray analysis in human normal oral keratinocytes (HNOKs) and oral squamous cell carcinoma (OSCC)-derived cell lines. To identify networks of interacting genes, the expression status of the microRNAs were evaluated and the candidate genes and determined microRNAs were examined by using Ingenuity Pathway Analysis software.We identified candidate 20 microRNAs for molecular targeting. Our findings may contribute to an understanding of key biologic functions and pathways of certain microRNAs associated with OSCC, and the expression status of miR-125b may play an important role in the progression and prognosis of this disease. These networks were also associated with Molecular Mechanisms of Cancer and Cell Cycle: GI/S Checkpoint regulations. In addition, the differential expression status of miR-125b may provide insights into the process of tumorigenicity and for planning new treatment strategies.

Academic Significance and Societal Importance of the Research Achievements

マイクロRNA、DNAなどの物質を内包しているエクソソームは血液、尿、唾液、骨髄などさまざまな体液中で確認されており、比較的容易に採取できる。このエクソソームに含まれる分子を解析することで、低侵襲かつ効率的に疾患の診断を行える可能性がある。また、エクソソームは内包する物質がもつ総合的な効果で細胞の性質を変化させる性質をもつ点で、既存の治療薬とは全く概念が異なる。エクソソーム、microRNAによる遺伝子制御による診断・治療法の開発の報告ほとんどない。以上のことから、独創的で非常にインパクトが強い研究であり、全く新しいタイプの診断、治療法の開発に役立つものと考えられる。