2022 Fiscal Year Final Research Report

Development of highly sensitive diagnostic and therapeutic methods using exosomes as a new biomarker for oral cancer

Research Project

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Project/Area Number	20K10126
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	Nihon University
Principal Investigator	SHINOZUKA Keiji 日本大学, 歯学部, 講師 (30431745)
Co-Investigator(Kenkyū-buntansha)	外木守雄日本大学, 歯学部, 教授 (50217519) 津田啓方日本大学, 歯学部, 准教授 (60325470) 市ノ川義美帝京大学, 医学部, 准教授 (20203101) 花上伸明帝京大学, 医学部, 准教授 (40385232) 小原研心大阪大学, 歯学部附属病院, 医員 (70598507)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	口腔がん / microRNA / エクソソーム / マイクロアレイ解析 / ネットワーク解析 / がん関連遺伝子
Outline of Final Research Achievements	In this study, we focused on a systematic analysis of oral squamous cell carcinoma (OSCC) exosomal miRNAs in order to develop new diagnostic and therapeutic methods. We performed microRNA microarray analysis in OSCC-derived cell lines and human normal keratinocytes (HNOKs) and identified 20 exosomal miRNAs that were differentially expressed in four OSCC-derived cell lines compared with those in HNOKs. To identify important functional networks and gene ontologies in OSCC, the identified miRNAs and their potential target genes were analyzed using Ingenuity Pathway Analysis. We detected six highly significant genetic networks which were enriched in cancer-related function. Four highly significant upstream miRNAs associated with tumorigenesis, tumor development, and regulation of the epithelial-mesenchymal transition. These analyses provide a comprehensive view of the functions of dysregulated exosomal miRNAs in OSCC, providing insight on its tumorigenesis and development.
Free Research Field	口腔外科学
Academic Significance and Societal Importance of the Research Achievements	タンパク、mRNA、miRNA、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、エクソソームはある１つの受容体や酵素を阻害するのではなく、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。このようなことから、本研究の成果は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。